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6/11/2013
ExamВ FindingsВ TheВ BloodyВ Masquerader
Polypoidal Choroidal Vasculopathy
JennyВ Z.В Xu,В O.D.
VAВ PaloВ AltoВ HealthВ CareВ System
PosteriorВ Segment
• VA
– OD 20/200+ PHNI
– OS 20/20
• Pupils
– ERRL, no APD
• Confrontations
– EOM: full OU
– VF: Full to finger counting OS, complete restriction OD temp, infra temp and superior temp • Anterior Segment: unremarkable OU, no rubeosis OU
• TONOMETRY:  10/12 mmHg @ 1417 Polypoidal Choroidal Vasculopathy
• Choroidal abnormality characterized by branching choroidal vascular network and vascular dilations of terminal choroidal vessels in shape of polyps
• Also classified as a subtype of  occult choroidal
neovascularization
• Initially described in 1982 by Yannuzzi “Idiopathic polypoidal choroidal vasculopathy”, also termed “posterior uveal bleeding syndrome”
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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PCVВ Epidemiology
• African American females
• More often in pigmented individuals such as Africans and Asians, but also found in Caucasians
• Age of diagnosis from 20s to 80s, most common between the age of 60 and 70 years
• 71% of PCV in Japanese population male and 75% of PCV in European population female
• Predilection for macular and peripapillary locations
• Bilateral in 14% Japanese population and 32% of Europeans diagnosed with PCV
Diagnosis
ClinicalВ Presentation
• Small to large branching of inner choroidal
vessels with multiple polypoidal structures • Variable sized serosanguineous detachment of the RPE and neurosensory retina • Subretinal hemorrhages, lipid exudation
• Subretinal fibrosis may result after resolution of serosanguineous complications
• Pigment epithelial hyperplasia and degeneration
ICGAВ andВ FAВ ofВ PCV
Gomi etВ al.,В ArchВ Clin Exp Ophthalmol,В 2007
EarlyВ phase
• ICGA is the gold standard for the diagnosis of PCV
• FA not helpful due to obscuration of the choroid by the RPE • ICG allows for higher transmittance of light to choroid and better resolution of the vasculature
• PCV definition by ICGA: single or multiple focal areas of hyperfluorescence arising from the choroid within the first 6 minutes after injection with or without associated vascular network. – Presence of orange‐red subretinal nodules with corresponding indocyanine green hyperfluoresence is pathognomonic of PCV
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
MidВ phase
ICGA
MidВ toВ lateВ phase
LateВ phase
FAВ 2
6/11/2013
OCTВ PathophysiologyВ KeaneВ PAВ etВ al.В Surv Ophthal,В 2012
Double layer sign: hyper‐reflective
layerВ beneathВ theВ RPE,В inner
boundary of Bruch’s membrane
choriocapillaris complex
Pathophysiology – Histology
• Increased hyalinization of choroidal vessels and massive exudation of fibrin and blood plasma; degeneration of small vessels with thickened basement membrane
• Hyalinization = extensive replacement of smooth muscle component by amorphous pseudocollagenous tissue of poorly defined nature,
orВ arteriosclerotic
changesВ thatВ areВ found
inВ theВ otherВ partsВ ofВ the
body
• Dilated venules and arterioles
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
• Mechanism not well understood – agreement concerning the origination of the polyps from the inner choroid
• Considered to be a subtype of exudative AMD (type 1, sub‐
RPE),В orВ asВ aВ separateВ entityВ dueВ toВ choroidal abnormalities
• AMD and PCV share similar and differing genetic factors involving the complement system
• According to Yannuzzi, PCV and AMD can be distinguished based on age, peripapillary locations of CNV, presence of soft drusen and ethnicity
• Similarity of PCV to CSC
Pathophysiology – Relationship to ARMD
• Massive exudation of fibrin and blood plasma raises choroidal tissue pressure to produce protrusion of choroidal tissues through weakened RPE and Bruch’s
• Choroidal neovascularization also found above the RPE in 2 out of 5 pathological specimens examined
• Neovascularization may arise from RPE and Bruch’s membrane breaks
• Overexpression of HTRA1 gene (responsible for extracellular matrix degradation) is associated with both macular degeneration and PCV
– Overexpression decreases integrity of the Bruch’s membrane
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Pathophysiology – Relationship to CSC
PCVВ theВ Masquerader
• Choroidal vascular hyperpermeability: multifocal hyperfluorescence in mid and late phases of ICGA
• Hyperpermeability in patients with PCV strongly associated with a history of CSC
• Eyes with PCV and CSC had thicker choroid compared different types of ARMD
• Increased thickness due to increased choriopapillary
permeabilityВ possiblyВ fromВ increasedВ hydrostaticВ pressure,В leadingВ alsoВ toВ RPEВ leaksВ andВ serousВ retinalВ detachments
• CSC and PCV both related to choroid congestion and leakage rather than simply diseases of the Bruch’s membrane
• Large subretinal hemorrhage and RPE atrophy may cause PCV to look like wet AMD
• In patients diagnosed with AMD, 4.8% to 23% found to have PCV instead, more commonly diagnosed in Japanese individuals
• Yannuzzi also reports PCV masquerading as CSC due to presence of serous pigment epithelial detachments and neurosensory retinal detachment
– Re‐diagnosed with PCV based on ICGA findings that distinguished the PEDs from choroidal polyps
NaturalВ History
• Highly variable
• Remitting and relapsing course of chronic, multiple recurrent serosanguineous detachments
• Approximately 50% of patients with posterior pole lesions have favorable visual outcome without treatment
• Persistent bleeding involving the macula resulting in vision loss in others
• Macular involvement ranges from 25 to 94% of patients
• Visual prognosis depends on the location of and size of lesions
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
Treatment:В CombinationВ Therapy
• EVEREST study: multi‐centered, double masked, ICGA guided, randomized controlled trial involving 61 patients evaluating best treatment modality • Percent of polyp regression
– Visudyne alone: 71.4%, VA improved by 7.5 letters
– 3 x 0.5 mg monthly Lucentis alone: 28.6%, VA improved by 9.2 letters
– Visudyne + Lucentis: 77.8%, VA improved by 10.9 letters, lowest rate of PDT – related hemorrhages • Recommend either combination therapy or ICGA guided PDT
• Anti‐VEGF: effective for reabsorption of subretinal fluid; monotherapy recommended if PDT contraindicated 4
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ManagementВ AlgorithmВ References
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•
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•
•
•
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•
•
•
•
•
•
•
•
•
•
•
Koh etВ al,В 2013
•
•
•
Yannuzzi LA.В Idiopathic polypoidal choroidal vasculopathy.В MaculaВ SocietyВ Meeting,В 1982,В Miami,В FL.
Yannuzzi LA,В FreundВ KB,В Goldbaum MВ etВ al.В Polypoidal choroidal vasculopathy masqueradingВ asВ centralВ serousВ chorioretinopathy.В Ophthalmology
2000;107(4):767‐77.
Lafaut BA, Leys AM, Snyers B, et al. Polypoidal choroidal vasculopathy in Caucasians. Graefes Arch Clin Exp Ophthalmol 2000;238:752–759.
Koh A,В LeeВ WK,В ChenВ LJ,В etВ al.В EVERESTВ study:В efficacyВ andВ safetyВ ofВ verteporfin PDTВ inВ combinationВ withВ ranibizumab orВ aloneВ versusВ ranibizumab
monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy. Retina 2012;32:1453–1464.
Ahuja RM, Stanga PE, Vingerling JR, et al. Polypoidal choroidal vasculopathy in exudative and haemorrhagic pigment epithelial detachments. Br J Ophthalmol 2000;84:479–484.
Gomi F, Sawa M, Mitarai K, et al. Angiographic lesion of polypoidal choroidal vasculopathy on indocyanine green and fluorescein angiography. Graefes Arch Clin Exp Ophthalmol 2007;245:1421–1427.
Koh A, Chen LJ, Chen SJ, et al. Polypoidal choroidal vasculopathy: evidence‐based guidelines for clinical diagnosis and Treatment. Retina, J Retinal and Vitreous Diseases 2013;33(4):686‐716
Imamura Y, Engelgert M, Iida T et al. Polypoidal choroidal vasculopathy: A Review. Surv Ophthalmol 2010; 55(6):501‐515
Koizumi H, Yamagashi T, Yamazai T et al. Relationship between clinical characteristics of polypoidal choroidal vasculopathy and choroidal vascular hyperpermeability. Am J Ophthalmol 2012:1‐9
Hayashi K, Hasegawa Y and Tokoro T. Indocyanine green angiograophy of central serous chorioretinopathy. Int Ophthalmol 1986; 9(1):37‐41
Hochman MA, Seery CM and Zarbin MA. Pathophysiology and management of subretinal hemorrhage. Surv Ophthalmol 1997; 42(3):195‐213
Birkholz ES, Johnson AT and Russell SR. Retinal Artery Macroaneurysm. EyeRounds.org. Posted July 7, 2010; Available from: www.EyeRounds.org/cases/113‐RAMA.htm
Kim SW, Oh J, Kwon SS et al. Comparision of choroidal thickness among patients with healthy eyes, early age‐related maculopathy, neovasculra age‐
related macular degeneration, central serous chorioretinopathy, and polypoidal choroidal vasculopathy. Retina J Retina and Vitreous Disease 2011; 31(9): 1904‐1911
Sato T, Kishi S, Watanabe G et al. Tomographic features of branching vascular networks in polypoidal choroidal vasculopathy. Retina, J of Retina and Vitreous Diseases 2007; 27(5)589‐594
Miki A, Honda S, Kojima H et al. Visual outcome of photodynamic theraphy for typical neovascular age‐related macular degeneration and polypoidal
choroidal vasculopathy over 5 years of follow up. Jpn J Ophthalmol 2013; 57:301‐307
Giovannini A, Amato GP. D�Altobrando E, Giuliani M. Optical coherence tomography (OCT) in idiopathic
polypoidal choroidal vasculopathy (IPCV). Doc Ophthalmol.1999;97(3‐‐4):367—71
Silva R. Neovascular Phenotypes: polypoidal choroidal vasculopathy. AMDBook. Last revision Oct 2011; available from: http://amdbook.org/content/neovascular‐phenotypes‐polypoidal‐choroidal‐vasculopathy
Keane PA, Patel PJ, Liakopoulos S et al. Evaluation of Ag‐related macular degeneration with Optical Coherence Tomography. Surv Ophthalmol 2012; 57(5)389‐414
Koizumi H, Yamagishi T,, Yamazaki T et al. Subfoveal choroidal thickness in typical age‐related macular degeneration and polypoidal choroidal
vasculopathy. Graefes Arch Clin Exp Ophthalmol 2011, 249:1123‐1128
Sato T, Kishi S, Watanabe G et al. Tomograhic features of branching vascular networks in polypoidal choroidal vasculopathy. Retina 2007, 27:587‐594
Glaucoma
ProgressiveВ OpticВ Neuropathy
NormalВ TensionВ Glaucoma
TheВ ProblemВ withВ LowВ Pressure
KristinВ Symon,В OD
UCВ BerkeleyВ SchoolВ ofВ Optometry
OcularВ DiseaseВ Resident
JuneВ 23,В 2013
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
• Degeneration of retinal ganglion cells and axons
• Loss of rim tissue
• Glaucomatous cupping
• Corresponding visual field defects that follow RNFL loss
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2nd LeadingВ CauseВ ofВ VisionВ LossВ Worldwide
• Over 40 million people worldwide (12.3%)
• Open angle glaucoma affects more than 2 million individuals in the US
• By 2020 there will be at least 3 million affected
• 50% of individuals go undiagnosed
NormalВ tensionВ glaucoma
• Open angle glaucoma with untreated IOP within the normal range (22 mmHg)
• 20‐39% of patients with OAG in the US and Europe
• Up to 30% of patients are under age 50
• The Collaborative Normal Tension Glaucoma Study (CNTGS) showed that a 30% decrease in IOP resulted in preservation of visual function
(Quigley,В 2004)
(MacDonald,В 2012)
ExaminationВ Findings
PatientВ DY
26В yo KoreanВ Female
Examination
Findings
OD
OS
BCVA
Refraction
20/20‐
‐5.75 ‐0.50 x 015
20/20‐
‐4.25 ‐1.50 x 155
Anterior Segment
Unremarkable
Unremarkable
IOPВ (@16:36)
18В mmHg
19В mmHg
Gonioscopy
Cilliary bodyВ 360
Cilliary bodyВ 360
Pachymetry
580В microns
573В microns
PresentedВ toВ clinicВ onВ 9/24/2010
CC:В decreasedВ peripheralВ vision
PreviousВ diagnosisВ ofВ Glaucoma
‐ diagnosed in Korea 8/2010
CurrentВ treatment:В Betoptic 1В gtt OUВ BID
Pre‐treatment IOP: OD 19 mmHg, OS 20 mmHg
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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OpticВ NerveВ andВ RetinalВ NerveВ FiberВ LayerВ Analysis
вњ•
HereditaryВ opticВ neuropathy
NormalВ В MRI
RuledВ outВ byВ history
вњ•
✕glaucomatous Non‐
MassВ lesionВ ofВ orbitВ orВ cranium
Trauma
cuppingВ andВ visualВ fieldВ defects
вњ•
HeavyВ metal
вњ•
Humphrey Visual Field 30‐2 Threshold
NormalВ TensionВ Glaucoma
• Visual field defects respecting horizontal
• Nasal step and arcuate defects
• Splinter hemorrhage at optic disc
IntracranialВ Mass
вњ•
Infection
Auto‐
immune • Neuroretinal rim pallor exceeds cupping
• Vertical alligned visual field defects
• Younger age
• Reduced visual acuity
LabВ WorkupВ Normal
(GreenfieldВ etВ al,В 1998)
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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DiscВ Hemorrhage
• Some studies report increased frequency of disc hemorrhages in normal tension glaucoma
• Controversial support of a vascular etiology for NTG • Jonas suggests that disc hemorrhages are found in most patients with glaucoma, however, they are more apparent in NTG due in part to different pressure mechanics at the optic nerve head • The CNTGS reported that a history of migraine HA and presence of Disc hemorrhage were both related with progression of glaucoma
Treatment
• Patient DY was started on Xalatan 1 gtt OU QHS
• Latanoprost (generic for Xalatan) is more effective at reducing IOP during sleeping hours than Timolol
(LiuВ etВ al,В 2003)
ProgressionВ ofВ NormalВ TensionВ Glaucoma
CNTGS
20%
80%
20%В ofВ patientsВ withВ NormalВ TensionВ GlaucomaВ showedВ progressionВ despiteВ aВ 30%В reductionВ inВ IOP
• Progression
– Visual field defect
– Neuroretinal rim thinning
– Nerve fiber layer defects
• Adjunctive topical therapy added: Ocular Perfusion
LowВ ocularВ vascularВ perfusionВ isВ aВ riskВ factorВ forВ glaucoma
• No tool to directly measure blood flow at the optic nerve head
• Extrapolate expected perfusion through a combination of systemic blood pressure and IOP
MeanВ ocularВ perfusionВ pressure:
MOPP = 2/3 [DBP + 1/3(SBP – DBP)] – IOP Diastolic ocular perfusion pressure:
DOPP = DBP – IOP
– Alphagan 1gtt OU BID
DOPPВ lessВ thanВ 55В mmHgВ =В twiceВ theВ relativeВ riskВ ofВ glaucoma
DBPВ =В diastolicВ BP SBPВ =В systolicВ BP
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
(Quaranta etВ al,В 2013)
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DiastolicВ OcularВ PerfusionВ PressureВ forВ DY
60
55
50
DOPPВ OD
45
40
DOPPВ OS
CutВ offВ 55
• Upward trend in DOPP with treatment
• However DOPP remains less than 55 mmHg
35
Neuroprotection
TheВ searchВ forВ pressureВ independentВ treatmentВ forВ glaucoma
• Aim to prevent or delay the death of neurons
PossibleВ Neuroprotective Agents
‐ antioxidants
‐ alpha‐2‐agonists
‐ N‐methyl‐D‐aspartate (NMDA) receptor antagonists
‐ glutamate inhibitors
‐ calcium channel blockers
‐ polyamine antagonists
‐ nitric oxide synthetase inhibitors
‐ Ginkgo biloba
‐ melatonin
‐ vitamin B‐12
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
CerebrospinalВ FluidВ Pressure
Examining the dark side • Trans‐laminar pressure differential is determined by the IOP and the orbital CSF‐pressure
• Trans‐laminar pressure is likely more important in glaucoma development than the transcorneal pressure measured by applanation
• Low CSF‐pressure increases the risk for glaucoma
(normal CSF‐P is 5 to 15 mmHg)
References
AGIS Investigators. The advanced glaucoma intervention study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmology 139, no. 4 (2000): 429‐440.
Bengtsson B, Leske MC, Yang Z, Heijl A, EMGT Group. Disc hemorrhages and treatment in the early manifest glaucoma trial. Ophthalmology 115, no. 11 (2008): 2044‐2048.
Chang EE, Goldberg JL. Glaucoma 2.0: Neuroprotection, neuroregeneration, neuroenhancement. Ophthalmology 119 (2012): 979‐986.
Choi J, Jeong J, Cho H, Kook MS. Effect of nocturnal blood pressure reduction on circadian fluctuation of mean ocular perfusion pressure: a risk factor for normal tension glaucoma. Investigative Ophthalmology & Visual Science 47, no. 3 (2006): 831‐836.
Coleman AL, Miglior S. Risk factors for glaucoma onset and progression.  Survey of Ophthalmology 53 (2008): S3‐S10.
Collaborative Normal‐Tension Glaucoma Study Group. The effectiveness of intraocular prssure reduction in the treatment of normal‐tension glaucoma.  Am J Ophthalmology 126, no. 4 (1998): 498‐505.
Ernest, PJ, Schouten JS, Beckers HJ, Hendrikse F, Prins MH, Webers CA.  An evidence‐based review of prognostic factors for glaucomatous visual field progression.  Ophthalmology 120 (2013): 512‐519.
Greenfield DS, Siatkowski RM, Glaser JS, Schatz NJ, Parrish RK.  The cupped disc: who needs neuroimaging?  Ophthalmology 105, no. 10 (1998): 1866‐1874.
Jonas JB, Wang N.  Association between arterial blood pressure, cerebrospinal fluid pressure and intraocular pressure in the pathophysiology of optic nerve head diseases.  Clinical & Experimental Ophthalmology 40 (2012): e233‐e234.
Krupin T, Liebman JM, Greenfield DS, Ritch R, Gardiner S.  A randomized trial of brimonidine versus timolol in preserving visual function: results from the Low‐
pressure Glaucoma Treatment Study.  Am J Ophthalmology 151, no. 4 (2010): 671‐681.
Liu CJ, Ko YC, Cheng CY, Chiu AW, Chou JC, Hsu WM, Liu JH.  Changes in intraocular pressure and ocular perfusion pressure after latanoprost 0.005% or brimonidine tartrate 0.2% in normal‐tension glaucoma patients.  Ophthalmology 109 (2012): 2241‐2247.
Liu JHK, Medeiros FA, Slight JR, Weinreb RN.  Comparing diurnal and nocturnal effects of brinzolamide and timolol on intraocular pressure in patients receiving Latanoprost monotherapy.  Ophthalmology 116 (2009): 449‐454.
Liu JHK, Zhang X, Kripke DF, Weinreb RN. Twenty‐four‐hour intraocular pressure pattern associated with early glaucomatous changes.   Invest Ophthalmol Vis Sci. 44 (2003): 1586‐90.
Macdonald, D.  Under pressure: a review of normal‐tension glaucoma.  Canadian Journal of Optometry 74, no. 4 (2012): 33‐44.
Medeiros FA, Lisboa R, Weinreb RN, Liebmann JM, Girkin C, Zangwill LM.  Retinal ganglion cell count estimats associated with early development of visual field defects in glaucoma.  Ophthalmology in press (2012): 1‐9.
Morgan WH, Yu DY, Balaratnasingam C.  The role of cerebrospinal fluid pressure in glaucoma pathophysiology: the dark side of the optic disc.  J Glaucoma 17, no. 5 (2008): 408‐413.
Quaranta L, Katsanos A, Russo A, Riva I.  24‐hour intraocular pressure and ocular perfusion pressure in glaucoma.  Survey of Ophthalmology 58, no. 1 (2013): 26‐
41.
Quigley HA, Broman AT.  The number of people with glaucoma worldwide in 2010 and 2020.  Br J Ophthalmology 90 (2006): 262‐267.
Ramli N, Nurull BS, Hairi NN, Mimiwati Z.  Low nocturnal ocular perfusion pressure as a risk factor for normal tension glaucoma.  Preventative Medicine in press (2012): 1‐3.
Ren R, Jonas JB, Tian G, Zhen Y, Ma K, Li S, Wang H, Li B, Zhang X, Wang N.  Cerebrospinal fluid pressure in glaucoma.  Ophthalmology 117, no. 2 (2010): 259‐266.
Shields, MB.  Normal‐tension glaucoma: is it different from primary open‐angle glaucoma?  Current Opinion in Ophthalmology 19 (2008): 85‐88.
Sung, K.R., S. Lee, S.B. Park, J. Choi, S.T. Kim, S.C. Yun, S.Y. Kang, J.W. Cho, M.S. Kook.  Twenty‐four hour ocular perfusion pressure fluctuation and risk of normal‐
tension glaucoma.  Integrative Ophthalmology & Visual Science 50, no. 11 (November 2009): 5266‐5274.
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D.G.В CaseВ Report
• 61 year old white male
– Relates sudden blurred vision OD for 1 month
NVG
StephenВ Chang,В O.D.
OptometryВ Resident
SierraВ NevadaВ HCS
RenoВ VA
JuneВ 23rd,В 2013
• Glaucoma suspect OU, pseudophake OU
• History of poor compliance with follow up visits
• Uncontrolled type 2 diabetes, hypertension, hyperlipidemia
– Family history of diabetes in father & grandfather
D.G.В ClinicalВ Data
• His vision was CF @ 3 ft OD, 20/25 OS with moderate myopic and astigmatic Rx
• 2+ RAPD OD, with inferior VF constriction detected on confrontation fields
• IOPs were 42/20 • NVI superior/temporally OD
• Scattered NVA in the superior/temporal quadrant.
• Hypotensive agents (brimonidine, cosopt) decreased the IOP to 25 OD within 2 hrs.
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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3В DaysВ Later
• Assessment:
– NVG secondary to CRVO OD
• Plan:
– Same day Ophthalmology consult/IFVA
– Pt started on maximum hypotensive gtts
– hypercoaguable state, CBC, Lipid profile, & Carotid U/S ordered Neovascular Glaucoma
• Late presentation of serious underlying systemic and ocular pathology
• Arises in response to profound retinal ischemia*
• Poor prognosis, highly resistant to treatment
• PRP performed OD
• IOP 32/16
• Due to AC cells/flare, pred forte added to gtt
regimen
• Scheduled for next available anti‐VEGF injection OD
NVGВ Definitions
• Wills Eye Manual
– Stage 1: NVI/NVA
– Stage 2: NVI/NVA + increased IOP
– Stage 3: 1, 2 + partial/complete angle closure
• Moraczewski et. al
– IOP > 21 mmHg associated with NVI/NVA
• Ehlers et. al
– IOP ≥ 4mmHg higher in eye with NV
– NVI/NVA with concurrent use of hypotensive gtts
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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Signs/Symptoms
•
•
•
•
•
•
•
•
•
•
•
Asymptomatic
DecreasedВ vision
Pain/photophobia
Redness
NeovascularizationВ ofВ theВ anteriorВ chamber
ElevatedВ intraocularВ pressure
AnteriorВ chamberВ cells/flare
CornealВ edema
Ectropion uveae
Synechial angleВ closure
CuppingВ ofВ theВ opticВ nerve
Treatment
•
•
•
•
•
•
•
•
•
•
Prevention
ReductionВ ofВ theВ IOP
Panretinal Photocoagulation
ParsВ plana vitrectomy (PPV)
Endolaser (EL) photocoagulation Anti‐VEGF agents*
Trabeculectomy
GlaucomaВ DrainageВ ImplantsВ (GDI)
Cyclophotocoagulation (CPC)
Cryoretinopexy
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
DifferentialВ Diagnosis
• Acute angle‐closure glaucoma
• Inflammatory open‐angle glaucoma
• Ocular ischemic syndrome
Pan‐Retinal Photocoagulation2
• Gold standard for initial treatment of anterior segment neovascularization due to retinal hypoxia
• Reduction of ischemic drive through fragmentation of blood column in all new vessels
• Noninvasive with few complications
• Effects are long‐lasting but often take weeks to occur
• Application of burns to cover a major portion of the retina in all quadrants
• 1200‐1600 burns of 500 micron spot size applied*
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TheВ roleВ ofВ Antiangiogenic Agents
• Regression of neovascularization occurs quickly but is temporary and recurrence is possible*
• Small studies (Iliev, Gheith) have shown that early treatment with intravitreal bevacizumab
(IVB)В improvedВ NVGВ outcomes
OutcomesВ ofВ TreatmentВ ofВ Neovascular GlaucomaВ withВ Intravitreal
Bevacizumab.  Moraczewski et. al.  Br. J Ophthalmol 2009; 93:589‐593.
• Bascom Palmer Eye Institute Standard of Care
– 1. IVB at time of diagnosis
– 2. PRP shortly thereafter
• Or Endolaser/PPV (if cloudy media)
– 3. Medical/surgical intervention (if necessary)
– If IVB is administered before formation of PAS, IOP may be controlled without surgical procedures9
ProposedВ TreatmentВ AlgorithmВ forВ Neovascular Glaucoma8
FollowВ upВ Schedule
• Every 2‐3 weeks1 (Hayreh, prospective study)
• Every 3‐4 weeks for the first 6 mos, less frequently thereafter.1 (Hayreh, clinically)
• NVI/NVA may occur quickly (days to weeks).10
• Rate at which PAS develops is remarkably variable (days to weeks).4
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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Ocular Neovascularization Associated with Central and Hemicentral Retinal Vein Occlusion.  Hayreh et al.  Retina 32:1553‐1565, 2012. Cumulative Probability of development of NV from onset of ischemic CRVO1
References
1.
2.
3.
4.
5.
6.
7.
Iris
Angle
Glaucoma
withinВ 1В month
16%
8%
4%
withinВ 2В months
26%
15%
11%
withinВ 3В months
33%
28%
20%
withinВ 6В months
49%
37%
29%
14.
withinВ 9В months
52%
39%
34%
15.
withinВ 5В years
63%
49%
39%
Posner‐Schlossman Syndrome and Inflammatory Glaucoma
8.
9.
10.
11.
12.
13.
16.
17.
Ocular neovascularization associated with central and hemicentral retinal vein occlusion.  Hayreh et al.  Retina 32:1553‐1565, 2012. Ophthalmic surgery: Principle & Practice. Spaeth, George. 1990. W.B. Saunders company.
Novartis Pharmaceuticals Australia Pty Limited. http://www.avastin‐hcp.com/bevacizumab/moa/proposed‐mechanism‐of‐action
Glaucoma, Chandler and Grant.  4th edition.  Epstein et. al.  1997. Chapter 225: Neovascular Glaucoma; Ophthalmology.  04/05/11; Fanous, Maher.  Erythropoietin levels in aqueous humor of patients with glaucoma.  Nassiri et. al.  Molecular Vision 2012; 18:1991‐1995.
Intraocular Pressure Abnormalities Associated with Central and Hemicentral Retinal Vein Occlusion.  Hayreh et. al.  Ophthalmology 2004; 111; 133‐141
Medical and Surgical Treatment of Neovascular Glaucoma.  Olmos, Lee.  International Ophthalmology Clinics.  Vol 51, No 3, 27‐36.
Outcomes of Treatment of Neovascular Glaucoma with Intravitreal Bevacizumab.  Moraczewski et. al.  Br. J Ophthalmol 2009; 93:589‐593.  Combination Intravitreal Bevacizumab/panretinal Photocoagulation vs Panretinal Photocoagulation Alone in the Treatment of Neovascular
Glaucoma.  Ehlers et. al.  Retina 28:696‐702, 2008.
Surgical Outcome of Intravitreal Bevacizumab and Filtration Surgery in Neovascular Glaucoma.  Kitnarong et. al.  Adv. Ther. 2008;25(5):438‐443.
Panretinal PhotocoagulationВ withВ SimultaneousВ Cryoretinopexy orВ Intravitreal Bevacizumab forВ Neovascular Glaucoma.В В Tatsumi etВ al.В В Graefes
Arch Clin Exp Ophthalmol.  2012. Mermoud A, Salmon JF, Alexander P, et al. Molteno tube implantation for neovascular glaucoma. Long‐term results and factors influencing the outcome. Ophthalmology. 1993;100:897–902.
Krupin T, Kaufman P, Mandell AI, et al. Long‐term results of valve implants in filtering surgery for eyes with neovascular glaucoma. Am J Ophthalmol. 1983;95: 775–82.
Anti‐VEGF Therapy for the treatment of glaucoma: a focus on ranibizumab and bevacizumab.  Park et. al.  Expert Opin Biol Ther. 2012 Dec; 12(12):1641‐7.
Surgical results of Ahmed Valve Implantation with Intraoperative Bevacizumab Injection in Patients with Neovascular Glaucoma.  Kyoung et. al.  J Glaucoma 2012;21:331‐336.
CombinedВ Intravitreal Bevacizumab andВ Trabeculectomy withВ Mitomycin CВ vs Trabeculectomy withВ Mitomycin CВ AloneВ forВ Neovascular
Glaucoma.  Takihara et. al.  J Glaucoma 2011;20:196‐201.
65В yearВ old male
• CC: “pressure” in eye
– Constant pressure and discomfort within OS since this morning with foggy vision, mild dull headache, and light sensitivity
• Medical History:
– Hypertension and hyperlipidemia medically‐controlled
TranВ Nguyen
VAВ PaloВ AltoВ HCS
PrimaryВ CareВ OptometryВ andВ LowВ VisionВ Rehabilitation
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
• Negative family medical history
• Family ocular history: father blind due to glaucoma
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HistoryВ Continued:
• Patient Ocular History:
– “Inflammatory glaucoma vs Posner‐Schlossman Syndrome OS”
– Resolved BRVO OS 2009 without complications
– Meibomian gland dysfunction
– Mild cataracts OU
– History of trauma, punched in OD when young
IntraocularВ Pressures:
02/26/13:
•20/65  @1438 Brimonidine, cosopt, latanoprost, prednisolone acetate 1%
•20/61  @1550 Brimonidine, cosopt, latanoprost, prednisolone acetate 1%
•20/60  @1611 Brimonidine, cosopt, latanoprost, prednisolone acetate 1%
•18/49  @1650
• ‐‐/55   @1850 Diamox 500mg po
• ‐‐/55  @2250  Anterior chamber paracentesis OS:
•‐‐/13 @2332  Diamox 250mg q6h, Vigamox qid, cosopt tid, brimonidine tid,  prednislone acetate 1% qid
• Ocular Medications:
– Cosopt bid OS with good compliance
• Last dose: twice this morning at 9:00am
Differential Diagnosis • Acute angle closure
• Neovascular glaucoma
• Hypertensive uveitic syndromes
–
–
–
–
•
•
•
•
•
Posner‐Schlossman Syndrome
Herpetic keratouveitis Fuch’s heterochromic iridocyclitis
CytomegalovirusВ iridocyclitis
Inflammatory/uveiticВ glaucoma
PrimaryВ openВ angleВ glaucoma
Non‐arteritic ishemic optic neuropathy
OpticВ neuritis
MasqueradeВ syndromes
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
Posner‐Schlossman Syndrome:
Recurrent,В unilateralВ anteriorВ uveitis withВ increasedВ IOP
MinimalВ conjunctival injection
CornealВ edema
FewВ nonpigmented keratic precipitates,В fewВ cellsВ andВ В mildВ flareВ reaction
• Angles open
• Pupils: iris heterochromia and anisocoria
• Trabeculitis
•
•
•
•
– Exact mechanism unknown
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PathogenesisВ ofВ PSS:
• Spectrum of inflammatory responses to members of herpesviridae family
– Cytomegalovirus
• Local antibodies
– Herpes simplex virus
“Inflammatory Glaucoma?"
• Persistent or recurrent IOP elevation 
anatomicalВ andВ physiologicalВ damageВ toВ ONH
• Higher suspicion for uveitic etiology with unilateral glaucomatous optic neuropathy
• Axonal and secondary retinal ganglion cell loss  Optic rim excavation & RNFL thinning
• Vascular/Autonomic imbalance
• HLA‐Bw54 positive Elevated IOP and Non‐glaucomatous Optic Neuropathy
• Optic atrophy & PSS
• NAION & PSS
Management:
• Nonsurgical treatment
– Corticosteroids
– Topical nonsteroidal antiinflammatories
– Aqueous suppressants • Flow = perfusion pressure
resistanceВ toВ flow
• Perfusion pressure = • Surgical intervention with medical failure or high risk cases
– Filtering surgery
Mean blood pressure – IOP
• Trabeculectomy with antimetabolites
• Glaucoma drainage implants
• Disc pallor in 20‐39% with acute angle closure
• Reduced S‐cone component of ERG in PSS
• Diagnostic labs and imaging when warranted
KimВ etВ alВ 2012.В KoreanВ JВ Ophthalmol
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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6/11/2013
IntraocularВ Pressures:
02/26/13:
•20/65  @1438 Brimonidine, cosopt, latanoprost, prednisolone acetate •20/61  @1550 Brimonidine, cosopt, latanoprost, prednisolone acetate •20/60  @1611 Brimonidine, cosopt, latanoprost, prednisolone acetate •18/49  @1650
• ‐‐/55   @1850 Diamox 500mg po
• ‐‐/55  @2250  Anterior chamber paracentesis OS:
• ‐‐/13 @2332  Diamox 250mg q6h, Vigamox qid, Dorz‐Tim tid, Alphagan tid, PF qid
02/27/13 13/40В @1230
02/28/13:  ‐‐/13 @0711 POD#1 s/p Ahmed OS
03/04/13: ‐‐/14  @1505 POD#5 Atropine qd OS, PF qid OS, Vigamox qis OS
03/18/13: 20/21В @1500В PFВ qid OS
04/04/13: 19/18В @1328В PFВ qid OS,В Timolol 0.25%В bidВ OS
05/14/13: 18/18В @1013В Timolol 0.25%В bidВ OS
05/28/13 Follow‐Up:
•VA: 20/25 OU
•1+ left APD
•IOP: 18/23 mmHg at 0815
C/D:В 0.35H/VВ В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В C/D:В 0.7H/0.75V
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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Summary: Posing as Posner’s?
HVFВ OSВ 2006В vs 2013:
• Previously thought to be “self‐limiting” and “benign”
– 26.4% develop glaucomatous damage – Jap et al
• CMV and HSV leading infectious etiologies for PSS – Still poorly understood
• Distinct clinical entities of HSV uveitic glaucoma and CMV iridocyclitis
• Multifactorial and complicated spectrum of conditions
• Prophylactic treatment in consideration of NAION associated with acute cyclitis episodes
• Important to monitor for glaucomatous and non‐
glaucomatousВ opticВ neuropathy
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Bloch‐Michel E, Dussaix E, Cerqueti P, Patarin D. Possible role of cytomegalovirus infection in the etiology of the Posner‐Schlossmann syndrome. Int Ophthalmol. 1987 Dec;11(2):95‐6.
Bodh SA, Kumar V, Raina UK, Ghosh B, Thakar M. Inflammatory glaucoma. Oman J Ophthalmol. 2011 Jan;4(1):3‐9.
Ceballos EM, Parrish RK 2nd, Schiffman JC. Outcome of Baerveldt glaucoma drainage implants for the treatment of uveitic glaucoma. Ophthalmology. 2002 Dec;109(12):2256‐60.
Chee SP, Jap A. Presumed fuchs heterochromic iridocyclitis and Posner‐Schlossman syndrome: comparison of cytomegalovirus‐positive and negative eyes. Am J Ophthalmol. 2008 Dec;146(6):883‐9.e1. Chee SP, Bacsal K, Jap A, Se‐Thoe SY, Cheng CL, Tan BH. Clinical features of cytomegalovirus anterior uveitis in immunocompetent patients. Am J Ophthalmol. 2008 May;145(5):834‐40. Epub 2008 Feb 6.
Contreras I, Rebolleda G, Noval S, Muñoz‐Negrete FJ.Optic disc evaluation by optical coherence tomography in nonarteritic anterior ischemic optic neuropathy. Invest Ophthalmol Vis Sci. 2007 Sep;48(9):4087‐92.
Contreras I, Noval S, Rebolleda G, Muñoz‐Negrete FJ. Follow‐up of nonarteritic anterior ischemic optic neuropathy with optical coherence tomography. Ophthalmology. 2007 Dec;114(12):2338‐44. Epub 2007 Aug 27.
Darchuk V, Sampaolesi J, Mato L, Nicoli C, Sampaolesi R. Optic nerve head behavior in Posner‐Schlossman syndrome. Int Ophthalmol. 2001;23(4‐6):373‐
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Dinakaran S, Kayarkar V. Trabeculectomy in the management of Posner‐Schlossman syndrome. Ophthalmic Surg Lasers. 2002 Jul‐Aug;33(4):321‐2.
Falcon MG, Williams HP. Herpes simplex kerato‐uveitis and glaucoma. Trans Ophthalmol Soc U K. 1978 Apr;98(1):101‐4.
Goldberg DE, Freeman WR. Uveitic angle closure glaucoma in a patient with inactive cytomegalovirus retinitis and immune recovery uveitis. Ophthalmic Surg Lasers. 2002 Sep‐Oct;33(5):421‐5.
Green RJ. Posner‐Schlossman syndrome (glaucomatocyclitic crisis). Clin Exp Optom. 2007 Jan;90(1):53‐6.
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Hayreh SS.  Anterior ischemic optic neuropathy. Clin Neurosci. 1997;4(5):251‐63.
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Hong C, Song KY. Effect of apraclonidine hydrochloride on the attack of Posner‐Schlossman syndrome. Korean J Ophthalmol. 1993 Jun;7(1):28‐33.
Horowitz J, Fishelzon‐Arev T, Rath EZ, Segev E, Geyer O. Comparison of optic nerve head topography findings in eyes with non‐arteritic anterior ischemic optic neuropathy and eyes with glaucoma. Graefes Arch Clin Exp Ophthalmol. 2010 Jun;248(6):845‐51. Epub 2010 Mar 6.
Irak I, Katz BJ, Zabriskie NA, Zimmerman PL.Posner‐Schlossman syndrome and nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol. 2003 Dec;23(4):264‐7.
Iwao K, Inatani M, Seto T, Takihara Y, Ogata‐Iwao M, Okinami S, Tanihara H.Long‐term Outcomes and Prognostic Factors for Trabeculectomy With Mitomycin C in Eyes With Uveitic Glaucoma: A Retrospective Cohort Study. J Glaucoma. 2012 Aug 14. Jap A, Sivakumar M, Chee SP. Is Posner Schlossman syndrome benign? Ophthalmology. 2001 May;108(5):913‐8.
Jones R 3rd, Pasquale LR, Pavan‐Langston D.Herpes simplex virus: an important etiology for secondary glaucoma. Int Ophthalmol Clin. 2007 Spring;47(2):99‐107
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Kim TH, Kim JL, Kee C.Optic disc atrophy in patient with Posner‐Schlossman syndrome. Korean J Ophthalmol. 2012 Dec;26(6):473‐7. Epub 2012 Nov 12.
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Li J, Ang M, Cheung CM, Vania M, Chan AS, Waduthantri S, Yang H, Chee SP. Aqueous cytokine changes associated with Posner‐Schlossman syndrome with and without human cytomegalovirus  2012;7(9):e44453. Epub 2012 Sep 13.
Maeda H, Nakamura M, Negi A. Selective reduction of the S‐cone component of the electroretinogram in Posner‐Schlossman syndrome. Eye (Lond). 2001 Apr;15(Pt 2):163‐7.
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Ozdal PC, Vianna RN, Deschênes J. Ahmed valve implantation in glaucoma secondary to chronic uveitis. Eye (Lond). 2006 Feb;20(2):178‐83.
Papadaki TG, Zacharopoulos IP, Pasquale LR, Christen WB, Netland PA, Foster CS.Long‐term results of Ahmed glaucoma valve implantation for uveitic glaucoma. Am J Ophthalmol. 2007 Jul;144(1):62‐69. Epub 2007 May 9.
Posner A., Schlossman A, Syndrome of unilateral recurrent attacks of glaucoma with cyclitis symptoms. Arch Ophthalmol, 39 (1948), pp. 517–535
Roth M, Simmons RJ. Glaucoma associated with precipitates on the trabecular meshwork. Ophthalmology. 1979 Sep;86(9):1613‐9.
SanghaВ SS.В PosnerВ SchlossmanВ syndrome.В Ophthalmology.В 2002В Mar;109(3):409.
Shazly TA, Aljajeh M, Latina MA.Posner‐Schlossman glaucomatocyclitic crisis. Semin Ophthalmol. 2011 Jul‐Sep;26(4‐5):282‐4. Sng CC, See JS, Ngo CS, Singh M, Chan YH, Aquino MC, Tan AM, Shabana N, Chew PT. Changes in retinal nerve fibre layer, optic nerve head morphology, and visual field after acute primary angle closure. Eye (Lond). 2011 May;25(5):619‐25.  Epub 2011 Mar 25.
Suh MH, Kim SH, Park KH, Kim SJ, Kim TW, Hwang SS, Kim DM. Comparison of the correlations between optic disc rim area and retinal nerve fiber layer thickness in glaucoma and nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol. 2011 Feb;151(2):277‐86.e1.  Epub 2010 Dec 18.
Sood GC, Kapoor S, Krishnamurthy MS, Reddy S, Sook M. Posner‐Schlossman syndrome surgical management. Eye Ear Nose Throat Mon, 55 (1976), pp. 29–32
Takahashi T, Ohtani S, Miyata K, Miyata N, Shirato S, Mochizuki M. A clinical evaluation of uveitis‐associated secondary glaucoma. Jpn J Ophthalmol. 2002 Sep‐Oct;46(5):556‐62.
Takusagawa HL, Liu Y, Wiggs JL.Infectious theories of Posner‐Schlossman syndrome. Int Ophthalmol Clin. 2011 Fall;51(4):105‐15. Teoh SB, Thean L, Koay E. Cytomegalovirus in aetiology of Posner‐Schlossman syndrome: evidence from quantitative polymerase chain reaction. Eye (Lond). 2005 Dec;19(12):1338‐40.
Wong M, Goldstein DA, Tessler HH; Presumed Fuchs heterochromic iridocyclitis and Posner‐Schlossman syndrome: comparison of cytomegalovirus‐
positive and ‐negative eyes author reply.  Am J Ophthalmol. 2009 Jun;147(6):1106‐7
Yamamoto S, Pavan‐Langston D, Tada R, Yamamoto R, Kinoshita S, Nishida K, Shimomura Y, Tano Y. Possible role of herpes simplex virus in the origin of Posner‐Schlossman syndrome. Am J Ophthalmol. 1995 Jun;119(6):796‐8.
Yang SY, Chen MJ, Chen KH, Li AF, Chou CK, Lee SM. Cytomegalovirus and herpes simplex virus as causes of bilateral anterior uveitis in an immunocompetent patient. J Chin Med Assoc. 2011 Jan;74(1):48‐50. Epub 2011 Jan 19.
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6/11/2013
Case Report
• 30 year old Caucasian female
Lights Out
By
Baljit Sohal, OD
Central California VA Health Care
Systems, Fresno CA
Case report continued
• VA
– c/o vision loss in the right eye for past three
days
– started with some blurriness and felt the
“lights went out” in that eye
• Medical and ocular history: unremarkable
Case continued…
• Slit lamp findings
– NLP OD, 20/25 OS sc
• Entrance testing
– Pupils: PERRL 2+APD OD
– Extraocular motility testing:
• FROM OU with mild pain on down gaze OD
– Confrontational visual field testing
– Conjunctiva: Temporal pinguecula OU
– Cornea: clear OU
– Anterior chamber: deep/quiet OU
– Lens: 1+ Nuclear sclerotic cataracts OU
– IOP: 15mmHg OD, 18mmHg OS by
Goldmann
• Unable to test OD, full OS
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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6/11/2013
Case continued…
• 60D undilated fundoscopic view
– 0.35V/0.40H OD, 0.50V/0.55H OS
– Pink and healthy nerves OU
– Macula flat (-)exudates/heme/srf OU
– Vessels were normal OU
Imaging continued…
• MRI of the orbits/brain
– Asymmetric enlargement, edema, and
enhancement of the right optic nerve
anterior to the chiasm involving the intraorbital
segment
– Brain parenchyma intact, without
characteristic white matter lesions of multiple
sclerosis
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
What to do?
• Assessment
– Retrobulbar optic neuritis OD
• Plan
– CT scan of brain and orbits followed by MRI
of brain and orbits with gadolinium
– RTC 7-14 days for recheck
Optic neuritis and clinical
features
• Acute
demyelinating
disease of the optic
nerve
• Isolated
neurological finding
or can be
associated with MS
• Monocular vision
loss
– 10% in both eyes
• simultaneous
• rapid succession
• Eye pain on eye
movements
• Visual field defect
– central scotoma
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Clinical features continued…
• Anterior optic
neuritis
• Retrobulbar optic
neuritis
– Papillitis
• hyperemia
• swelling of the disc
– Blurry disc margins
– Distended veins
– APD
– Color vision
– Normal
fundoscopic
examination
– Disc pallor after
few weeks
– APD
– Color vision
– Most common
Optic Neuritis Treatment Trial
• Results
– Patients receiving IV methylprednisolone
followed by oral prednisone recovered vision
faster than placebo
• Final visual outcome was only slightly better at 6
mo
– Oral prednisone alone provided no benefit in
rate of recovery or final outcome at six
months
Optic neuritis treatment
• Optic Neuritis Treatment Trial
– Corticosteroids in the treatment of acute optic
neuritis
– 457 patients with acute optic neuritis
• Oral prednisone x 14 days(1mg per kg of body
weight per day)
• Intravenous methylprednisolone (1g/day for 3
days) followed by oral prednisone for 11 days
• Oral placebo
MRI and MS
• Typical brain lesion plaques that are seen
in patients with MS
– Ovoid
– Periventricular
– white matter lesions
– Larger than 3mm
• ONTT follow up showed the risk of MS
after Optic neuritis
• higher rate of new attacks
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Optic Neuritis Treatment Trial
• Cumulative probability of developing MS
by 15 year examination was 50%
– Strongly related to presence of lesions on the
baseline brain MRI
– No difference among treatment groups
• Risk of developing MS was highest in the
first five years overall
• In patients w/o lesions, risk was higher for
women(16%), or with retrobulbar ON
What is MS
• Autoimmune
• Demyelinating disorder of the nervous
system
– Commonly manifested with visual involvment
• Chronic relapsing and remitting, episodic
disease
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
ONTT and MS continued
• No baseline MRI lesions
– Approx 15% developed MS during 5 years
– 25% developed MS during 15 year follow-up
• One or more lesions
– Approx 42% developed MS during 5 years
– 72% developed MS during 15 year follow-up
• Low risk of MS
– no MRI/brain lesions,
– male gender
– optic disc edema and atypical optic neuritis
Multiple sclerosis symptoms
• Numbness or weakness in one or more
limbs
• Double vision or blurring of vision
• Tingling or pain in parts of your body
• Electric-shock sensations that occur with
certain head movements
• Tremor, lack of coordination or unsteady
gait
• Slurred speech
• Fatigue
• Dizziness
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More ocular involvement
• Isolated cranial nerve palsies
– Mostly CN 6
• Internuclear Ophthalmoplegia
• Defects with Saccades and Pursuits
• Nystagmus
– INO, vestibular, pendular, gaze-evoked
• Retinal periphlebitis (10-39%)
– Perivascular exudation, hemorrhage, and
retinal venous sheathing
“Worst Headache of my life"
Treatment and Management of
Pituitary Macroadenoma
References
•
•
•
•
•
•
•
•
Mathews, Michaela. Nonarteritic anterior ischemic optic neuropathy. Current Opinion
in Ophthalmology. Lippincott Williams & Wilkins. 2005
Beck, Roy, M.D, et al. A Randomized, Controlled Trial of Corticosteroids in the
Treatment of Acute Optic Neuritis. The New England Journal of Medicine.
Massachusetts medical society. 1992
Myelitis Association. The Transverse Myelitis Association, Optic Neuritis. TMA. 2012
Osborne, Benjamin, et al. Optic Neuritis: Pathophysiology, Clinical Feautures, and
Diagnosis. Wolters Kluwer Health. Uptodate. 2013
Gal, Robin, et al. Visual Function More Than 10 Years After Optic Neuritis:
Experience of the Optic Neuritis Treatment Trial. American Journal of Opthalmology.
Elsevier Inc, 2004
Gal, Robin, et al. Multiple Sclerosis Risk after Optic Neuritis: Final Optic Neuritis
Treatment Trial Follow up. Arch Neurol. 2008 June; 65(6):727-732
Volpe, Nicholas, et al. Optic Neuritis and risk of MS: Differential diagnosis and
management. Cleveland clinic Journal of Medicine. March 2009 vol 76 3 181-190
Chen, Ling, et al. Ocular Manifestations of Multiple Sclerosis. Current Opinion in
Ophthalmology 2005. 16:315 -320
D.M
п‚ћ 64 yo WM presented to
outside Emergency
Department
 “Worse headache of my life”
Tresca Truong
Optometry Resident
VA Sierra Nevada Health Care SystemReno 6/23/13
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
п‚ћ HPI
п‚—
п‚—
п‚—
п‚—
п‚—
Crushing, alleviated by nothing
Nausea
Vomiting
Woke him from sleep
No altered mental status, fever
or weight loss
п‚— No vision loss
п‚ћ Systemic medical history
п‚— Chronic pain
п‚— Colon polyps
п‚— Bipolar Disorder
п‚— Anxiety
п‚ћ
Medications: Oxycodone HCL,
Morphine
п‚ћ Social history
п‚— Lives alone
п‚— (-) smoking
 (+) alcohol: “few times a week”
23
6/11/2013
Differential Diagnosis
•
•
•
•
•
•
•
Pituitary Gland
Migraine
Tension headache
Cluster headache
CVA
Intracerebral hemorrhage
Intracranial mass
Sinusitis
Reno VA
п‚ћ Right superior visual field
loss, losing 11 lbs in one
month, confusion, difficulty
with memory’
п‚ћ Patient Medical History
п‚ћ
п‚ћ
п‚ћ
п‚ћ
п‚ћ
п‚ћ
п‚ћ
п‚ћ
Anxiety
Psychosocial disorder
Mood disorder
Low back pain
Gout
Medication seeking behavior
Hypercholesteremia
Hypogonadism
п‚ћ
п‚ћ
Medications
п‚ћ Allopurinol, calcium, docusate,
morphine, oxycodine, respiridone,
simvastatin, tamulosin
Social History
п‚— Smoking: quit 40 years ago
п‚— EtOH: 3-4x a week, sometimes 6 pack
of beer/day, with wine at night
п‚— Illicit Drugs: history of cocaine and
marijuana use
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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6/11/2013
10mm
Treatment
1,2,3
• Monitor if <10mm
• Endoscopic
Transphenoidal Tumor
Resection
• Radiotherapy only if
residual tumor tissue
left over after surgery
• Labs must be ordered to
determine if secreting or
non-secreting.
–
–
–
–
–
–
–
–
TSH
Thyroxine
GH
Prolactin
Estrogen/Testosterone
ACTH
LH
ADH
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
Pituitary Adenoma
• Common benign tumors 1,2,3
• 10-12% of adult intracranial
neoplasms 2,5,8
• Categorization 6,7,8
– Size (micro vs macro)
• Stage 1 <10mm
• Stage 2 >10mm
• Stage 3 locally invasive
• Stage 4 diffusely invasive
– Secretions (nonfunctioning vs
functioning)
• Incidence rates 8,9
– Higher in women in early life
– More common with men later in
life
– Higher in African American and
lowest in American
Indians/Alaskan Natives
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6/11/2013
Stage of Improvement
11
Visual Disturbance
1,3,7,10
• Stage One (surgery to one week)
– Visual Field Defects 96%
• Unilateral 32.9%
• Bilateral 67.1%
• Rapid recovery, result of recovery of nerve conduction by
removal of physiologic conduction block
– Visual Acuity
63%
– Color vision
38.7-56%
– Optic Atrophy
28-49%
– Ptosis
6%
– Diplopia
10%
– Nerve palsy
2%
• Stage Two (1 month to 4 months)
– Delayed recovery is thought to be the result of remyelination of
decompressed optic pathways
• Stage Three
Positive
•
•
•
•
•
Young age
Short duration of symptoms
Good acuity
Small field loss
Normal color vision
– Late recovery over months to years. Not well studied
Negative
• Optic disc pallor
• High MD absolute value
• Long duration of symptoms
• Large Tumor size
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
Complete
Recovery
Partial Recovery
Unchanged
Visual Field (95%)
48.9%
46.8%
4.3%
Visual Acuity
33.35%
33.35%
33.3%
Color Vision
30%
52.8%
(-)
Optic Disc Pallor
16.9%
50%
(-)
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6/11/2013
11/19/2012
Follow-up
Follow-up
• Biopsy:Non-functioning
•
Pt reported intermittent left lower VF
defect
• Given size of mass, will likely need radiation
•
VA: 20/60 PH 20/30 OD
20/40 PH 20/30-1 OS
• Start on testosterone
•
(-)APD
•
Ishihara: 14/14 OU
•
Confrontational fields: left lower quadrant
VF constriction
•
EOMs revealed full ductions and versions
Anterior Segment
• Unremarkable
Posterior Segment
• C/Ds: 0.20h/v OU
• Macula: normal
• Vessels: normal caliber
• Periphery: (-)holes and detachments
References
What can we do?
1.
1.
2.
3.
4.
5.
Filters to enhance contrast
Low vision exam for devices that may help with magnification
Prisms or mirrors to compensate for field loss or diplopia
Vision therapy
Visual fields important to see if they meet state law requirements for
driver’s license.
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
Barzaghi et al. Prognostic Factors of Visual Field Improvement after Trans-sphenoidal Approach for Pituitary
Macroadenomas: Review of the Literature and Analysis by Quantitative Method. NeuroSurgery Review. 2012.
35:369-379
2. Dhasmana et al. Visual Fields at Presentation and After Trans-Sphenoidal Resection of Pituitary Adenomas. J.
Ophthalmic Vis Res. 2011. 6(3):187-191.
3. Schmalisch et al. Predictors for Visual Dysfunction in Nonfunctioning Pituitary Adenomas-Implications for
Neurosurgical Management. Clinical Endocrinology. 2012. 77:728-734.
4. Pituitary Macroadenoma Endonasal Endoscopic Removal. St. John’s Health Center.
5. Lee et al. The Volume of Tumor Mass and Visual Field Defect in Patients with Pituitary Macroadenoma. Korean J.
Ophthalmology. 2011. 25(1): 37-41.
6. Daly et al. The Epidemiology and Management of Pituitary Incidentalomas. Hrm. Rs. 2007 68(5): 195-198
7. De Aguiar Ribeiro Cury et al. Non-functioning Pituitary Adenomas: Clinical Feature, Laboratorial an Imaging
Assessment, Therapeutic Management and Outcome. Arq Bras Endocrinol Metab. 2009. 53 (1): 31-39.
8. Caputo et al. Gender Differences in Presentation and Outcome of Nonfunctioning Pituitary Macroadenomas. Clinical
Endocrinology. 2013. 78:564-570.
9. McDowell et al. Demographic Differences in Incidence for Pituitary Adenoma. Pituitary. 2011. 14(10):23-30.
10. Poon et al. Patterns of Visual Loss Associated with Pituitary Macroadenomas. Aus and NZ Journal of Ophth. 1995.
23(2):107-115.
11. Kerrison et al. Stages of Improvement in Visual Fields After Pituitary Tumor Resection. Am. Journal of Ophth.
2000. 130 (6): 813-820.
27
6/11/2013
DifferentialВ DiagnosisВ ofВ anВ EsotropiaВ withВ anВ AbductionВ DeficitВ inВ Infants
JillВ Kronberg,В OD
JuneВ 23,В 2013
3‐Year‐Old Male
IncidenceВ ofВ Strabismus
• 3‐5% of children affected by strabismus
• Esotropia appears 3‐5 X more than exotropia in children
• 50% of childhood esotropia has an accommodative component
• After age 4 the prevalence of exotropia exceeds esotropia
• Intermittent exotropia is the most common type of exotropia
ExamВ Findings
• Abduction deficit
• Second Opinion
•
•
IntolerantВ ofВ spectacleВ wear
CurrentВ Rx:
• OD: ‐1.25 DS
• OS: ‐2.00 DS
• Personal Medical History
•
•
•
•
Born past‐term
MildВ asthma
NICUВ forВ breathingВ difficulty
NoВ medications
RefractiveВ Findings
VisualВ Acuity
• Cardiff @ 100 cm
• OD: 0.6/1.9 M ~20/63
• OS: 0.6/1.2 M ~20/40
• OU: 20/50
Retinoscopy
• OD: plano ‐1.25 x 090
• OS: plano – 1.50 x 090
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
– OD: ‐2 restriction
– OS: ‐4 restriction
• Compensatory head posture
• Ocular posture: appeared aligned in primary gaze
• Contrast sensitivity: 1.6% Michelson Contrast
• Normal color vision
• Anterior Segment: Unremarkable
• Posterior Segment: Unremarkable
DifferentialВ Diagnosis
• Sixth Cranial Nerve Palsy
• Type I Duane Syndrome
• Infantile Esotropia
• Accommodative Esotropia
• Mobius Syndrome
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6/11/2013
SixthВ CranialВ NerveВ Palsy
• Sudden onset inward eye‐turn
• Limited aBduction
• Head‐turn towards affected side
– Eliminates diplopia
Etiology
• Most common cause: Intracranial tumor
• Post‐vaccination
• Post‐febrile infection
• Hydrocephalus
• Trauma
IntracranialВ tumors
• Worst prognosis in symptoms
– Large restriction of abduction
– Most likely to be bilateral
• Associated neurologic symptoms
– Headache, ataxia, and other cranial nerve palsies
– Onset within one week of strabismus • Types of tumors
– Brainstem glioma
– Cholesterol granuloma of petrous bone
– Eosinophilic granuloma of petrous bone
http://www.meddean.luc.edu/lumen/MedEd/grossanatomy/h_
n/cn/cn1/images/cn‐6.jpg
http://avserver.lib.uthsc.edu:8080/Medicine/eye_exam/SixthNervePalsy.jpg
Prognosis
TypeВ IВ DuaneВ Syndrome
• Mechanism is unknown
• Full recovery expected in benign palsy
• Spontaneously resolves within 6 months
Treatment
•
•
•
•
ThoroughВ caseВ history
AssociatedВ neurologicВ symptoms:В MRI/refer
SpontaneousВ resolution
NoВ resolutionВ postВ 6В months
– Botulinum toxin
– Surgery – better outcome closer to onset
• Congenital disorder affecting ocular motility
• Characterized by:
– Limited aBduction
– Narrowing of the intrapalpebral fissure on adduction
– Retraction of the globe on adduction
http://www.mrcophth.com/ocularmotility/duaneb.JPG
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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•
•
•
•
Characteristics
TypeВ IВ DuaneВ SyndromeВ isВ mostВ commonВ classificationВ ofВ DuaneВ syndrome
FemaleВ >В male
PossibleВ strabismusВ inВ primaryВ position
OSВ moreВ frequentlyВ affectedВ inВ aВ unilateralВ presentation
Etiology
• Absence of abducens nucleus
• Anomalous innervation by CN III to the lateral rectus muscle
– MR & LR contract simultaneously causing globe retraction
• No associated degeneration associated absence of nucleus
Prognosis/Treatment
• Prognosis:
– Non‐progressive
• Treatment
– Strabismus surgery if strabismus in primary gaze
– Best outcome with bilateral esotropia Duane syndrome
Prognosis/Treatment
InfantileВ Esotropia
• Previously known as congenital esotropia
– Not initially present in neonates
• Presents before 6 months of age
• Large angle esotropia – (>40 prism diopters)
• Vertical misalignment
– Dissociated vertical deviation (DVD)
– Over‐action of the inferior oblique
• Abduction obtainable
http://health‐
7.com/Atlas%20of%20Pediatric%20Physical%20Diagnosis/Esodeviations/
1
AccommodativeВ Esotropia
• Over‐convergence associated with accommodative system
• Three origins of accommodative esotropia
• Prognosis
– Amblyopia treatment
• Good visual acuity outcomes
• Unlikely to appreciate stereopsis
• Treatment
– Treat amblyopia
– Surgery
• Contraindicated before four months of age
• Degree of esotropia may resolve before six months of age
• Correct refractive error before surgery
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
– Hypermetropia
– High ratio of accommodative convergence to accommodation (AC/A)
– Combination of hypermetropia and AC/A ratio
TypesВ ofВ AccommodativeВ Esotropia
• Partially accommodative
– Residual esotropia with full (+) Rx
– Hypothesized: secondary anatomical contracture of medial rectus
• Fully accommodative
– Corrected with full (+) Rx
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6/11/2013
Prognosis/Treatment
Mobius Syndrome
•Unilateral or Bilateral                CN VI Palsy
•Impairment of aBduction
• Prognosis: Excellent
– Potential for stereopsis
– Normal visual acuity
• Treatment
– Treatable with glasses / bifocals
• Ensure add bisects the pupil!!
– Surgery contraindicated
•CN VII Palsy
•Non‐progressive
CharacteristicВ Appearance
•
•
•
•
Mask‐like facies
Drooling
Lagophthalmos
AssociatedВ limbВ anomalies
– Club foot, fused digits, absence of portion of limb
– Poland’s anomaly
• Syndactyly + malformation of unilateral pectoralis muscle
http://bjo.bmj.com/content/86/8/923.full
http://www.mastersinhealthcare.net/blog/2010/10‐diseases‐you‐didnt‐know‐existed/
Etiology
• Unknown
• Hypothesis
– Transitory interruption of fetal blood supply to brain stem
• Secondary to tetratogen exposure during the first trimester
• Tetratogen: gestational hyperthermia, electric shock, abuse of benzodiazepines, alcohol, etc.
Prognosis/Treatment
DifferentialВ Summary
•
•
•
•
•
Mobius пѓЁ Rare,В allowВ headВ movement
VIВ CranialВ NerveВ PalsyВ пѓЁ ReferВ OMD/ConsiderВ MRI
Infantile Esotropia  Co‐management (Provide Rx)
Accommodative Esotropia  Full (+), don’t refer
Duane Syndrome  Relax, it’s stable!
• Prognosis: Good
– Stable condition
• Treatment
– Allow patient to move head into restricted fields
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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The rest of the story…
• Remaining patient history
– Mild left facial nerve palsy
– No limb anomalies
• Previously diagnosed with Mobius syndrome at 8 months of age
References
•
•
•
Assessment
• Mobius syndrome
– Previously diagnosed
• Regular astigmatism
•
•
•
•
•
•
•
Plan
• Discontinue spherical myopic spectacle wear
• Allow pt to move his head
• Inform pediatrician/physical therapists to allow head movement
• Seek care yearly
•
•
•
•
•
•
•
•
•
•
Batra, Noopur N., CO. "Comparison of Primary Position Measurements and Abduction Deficit Between Type I Duane Syndrome and Sixth Cranial Nerve Palsy." Journal of Neuro‐Ophthalmology 31 (2011): 117‐20. Print. Birch, E., D. Stager, K. Wright, R. Beck, and Pediatriceyediseaseinvestigator. "The Natural History of Infantile Esotropia during the First Six Months of Life1, 2." Journal of American Association for Pediatric Ophthalmology and Strabismus 2.6 (1998): 325‐28. Print. Birth, Eileen E. "Stereoacuity Outcomes Following Treatment of Infantile and Accommodative Esotropia." Optometry & Vision Science 86.6 (2009): 647‐
52. Print. Briegel, W. "Neuropsychiatric Findings of Mobius Sequence ‐ a Review." Clinical Genetics 70.2 (2006): 91‐97. Print. Carta, Arturo, MD. "Ophthalmologic and Systemic Features in Mobius Syndrome: An Italian Case Series." Ophthalmology 118.8 (2011): 1518‐523. Print. Cheng, Daryl R. "Recurrent 6th Nerve Palsy in a Child following Different Live Attenuated Vaccines: Case Report." BMC Infectious Diseases 12.105 (2012): 1‐5. Print. Dotan, Gad. "The Role of Neuroimaging in the Evaluation Process of Children with Isolated Sixth Nerve Palsy." Child's Nervous System 29 (2013): 89‐92. Print. Hutchinson, Amy. "Refractive Surgery for Accommodative Esotropia: Past, Present, and Future." European Journal of Ophthalmology 22.6 (2012): 871‐
77. Print. Ing MR. “Long‐term follow‐up of congenital esotropia in a population based study.” Journal of the American Association for Pediatric Opthalmology and Strabismus 2009: 427
Johansson, Maria, MD. "Autistic Spectrum Disorders in Mobius Sequence: A Comprehensive Study of 25 Individuals." Developmental Medicine & Child Neurology 43 (2001): 338‐45. Print. Kang, N., and J. Demer. "Comparison of Orbital Magnetic Resonance Imaging in Duane Syndrome and Abducens Palsy." American Journal of Ophthalmology 142.5 (2006): 827‐34.e2. Print. Khan, A., and D. Oystreck. "Clinical Characteristics of Bilateral Duane Syndrome." Journal of American Association for Pediatric Ophthalmology and Strabismus 10.3 (2006): 198‐201. Print. Kim, Wook Kyum. "The Analysis of AC/A Ratio in Nonrefractive Accommodative Esotropia Treated with Bifocal Glasses." Korean Journal of Ophthalmology 26.1 (2012): 39‐44. Print. Lee, Tae‐Eun. "Accommodative and Tonic Convergence and Anatomical Contracture in Partially Accommodative and Non‐accommodative Esotropia." Ophthalmic & Physiological Optics 32 (2012): 535‐38. Print. Merino, Pilar, MD. "Etiology and Treatment of Pediatric Sixth Nerve Palsy." Journal of American Association for Pediatric Ophthalmology and Strabismus
14.6 (2010): 502‐05. Print. Mohney, B. "Common Forms of Childhood Strabismus in an Incidence Cohort." American Journal of Ophthalmology 144.3 (2007): 465‐67. Print. Mohney, Brian G., Chrystia C. Lilley, Amy E. Green‐Simms, and Nancy N. Diehl. "The Long‐term Follow‐up of Accommodative Esotropia in a Population‐
based Cohort of Children." Ophthalmology 118.3 (2011): 581‐85. Print. Olitsky, Scott E., and Leonard B. Nelson. "Strabismus Disorders." Pediatric Clinical Ophthalmology: A Color Handbook. London: Manson, 2012. 51‐57. Print. Pollard, Zane F., MD. "Accommodative Esotropia During the First Year of Life." Archives of Ophthalmology 94 (1976): 1912‐913. Print. Sachdeva, Virender, MS. "Surgical Management of Bilateral Esotropic Duane Syndrome." Journal of American Academy of Pediatrics Ophthalmology and Strabismus 16.5 (2012): 445‐48. Print. Terzis, Julia K., and Katerina Anesti. "Developmental Facial Paralysis: A Review." Journal of Plastic, Reconstructive & Aesthetic Surgery 64.10 (2011): 1318‐333. Print.  Case Report: AC
• 91 y.o. Hispanic male
• CC: Severe eye pain and sudden vision loss OS
OcularВ IschemicВ Syndrome
LavenderВ Orr,В O.D.
VACCHCSВ OptometryВ Resident
JuneВ 23,2013
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
– Began two days ago without relief
– Seen by outside general ophthalmologist
• Elevated IOP 60‐70mmHg OS
• Avastin intraocular injection
• Prescribed topical anti‐hypertensives & oral Diamox
• Pertinent medical Hx
–
–
–
–
–
CongestiveВ heartВ failure
COPD
TransientВ ischemicВ attack
Hypertension
Obesity
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ExamВ Findings
• Normal Findings OD
• BCVA:
– OS: HM
• Pupils:
– OS: mydriatic pupil
• Confrontations:
– OS: Constricted 360 • Biomicroscopy OS
– 2‐3+ diffuse microcystic
edema
– Formed AC
– Definite 360 iris rubeosis
• Tonometry:
– 16/59mmHg @11:11am
– Oral acetazolamide
administeredВ w/topicalВ antihypertensives &В Muro
128В ung
– ‐‐/52mmHg @ 12:23pm
– Additional dose of aforementioned therapy
A&P
• Plan:
• Assessment:
– Neovascular glaucoma OS
• Acute ocular hypertensive crisis
– Most likely etiologies • OIS
• CRAO
• old CRVO
• Fundus view:
– Attenuated arteries OS
– No dilated/tortuous veins
– No obvious intraretinal
hemorrhaging
Neovascular glaucoma
• What is NVG?
– Chronic, progressive ocular ischemia
– Radical IOP increase
– Severe vision loss
• Common causes:
– DM
– CRVO
– OIS
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
– Acetazolamide 250mg PO QID
– Anti hypertensives
w/atropineВ BID
– Order carotid ultrasound
– Lab testing: ESR, CRP, CBC, Chem 7
– RTC 1 week
CRAO
• Source:
– Retinal emboli
• Symptoms:
– Sudden, painless loss of vision • Signs:
– (+) APD
– Attenuated arteries
– Cherry red spot in acute phase
– Emboli
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IschemicВ CRVO
• Source:
OcularВ ischemicВ syndrome
• Source
– Thrombus formation
– Carotid artery occlusion
• Symptoms:
• Symptoms
– Sudden, painless loss of vision
– Eye pain & decreased acuity
• Signs
• Signs
– (+) APD
– Widespread hemorrhaging – Dilated/tortuous retinal veins
– Mid peripheral intraretinal hemorrhages
– Dilated retinal veins without tortuosity
InВ officeВ followВ upВ #1
• Good compliance, no pain
• Lab Testing:
– Normal, mildly elevated ESR
• Tonometry:
– ‐‐/40mmHg
• Carotid Ultrasound
• Same day PRP w/ retinal specialist
• Vascular consultation
–
–
–
–
BenefitsВ ofВ CEA
MRA
325В mgВ aspirinВ daily
Statin medication
– Greater than 70% stenosis to near occlusion bilaterally
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
OcularВ ischemicВ syndrome
• Rare & severe form of ocular ischemia
– 7.5/1,000,000
• Common symptoms
– Ocular pain
– Amaurosis fugax
– TIA symptoms
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DemographicsВ &В Etiology
• Commonly seen in • Hemodynamically
patientsВ overВ theВ ageВ ofВ significantВ ipsilateral
65
internalВ carotidВ arteryВ occlusion
• Men 2x more than – Rare: occlusion of women
ophthalmic artery or • Other chronic illnesses
occlusion along aortic • 5 year mortality rate of arch
40%
– Greater than 90%
DiagnosisВ &В Treatment
• Ophthalmodynamometry
– Decreased central retinal artery perfusion
• Fluorescein angiography
– Delayed & patchy choroidal
filling
• Carotid ultrasound
– Benefit of MRA
– High grade stenosis of 70‐
99%
– 92/1,415 = 6.5%
– 2.0% ‐ disabling stroke or death
– Gold standard treatment
– Successful for preventing progression of chronic ocular ischemia
– Risky!
– Obstruction <99%
• Early diagnosis is critical!
Crest:В CEAВ vs CAS
NASCET
• The North American Symptomatic Carotid Endarterectomy Trial
• Carotid Endarterectomy
(CEA)
• The Carotid Resvascularization
Endarterectomy vs
StentingВ Trial
• Overall, no significant difference at four years
– >70 years: CEA
– <70 years: CAS
– Stroke
• 2.3% vs 4.1%
– Myocardial infarction
• 2.3 vs 1.1%
– Death
• 0.3% vs 0.7%
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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BEWARE!!
• Increased risk of CRAO
• Immediate and rapid changes often affects ocular structures
– Relative hypotony
– Rapid increase in IOP
– Pain!!
FightingВ ischemia
• Best to manage with:
• PRP – Anti‐hypertensives that decrease aqueous production
– Topical cycloplegic
– Constant solution
• Anti VegF
– Temporary solution
– Good in cases of media opacity
• PRP + anti VegF
– Increased success rate for glaucoma surgery References
ClinicalВ pearls
•
• Early & prompt diagnosis is key to prevent fatal effects
• Work closely with PCP
&В otherВ specialists
• Patient education
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
Back, Martin et al. Magnetic resonance angiography is an accurate imaging adjunct to duplex ultrasound scan in patient selection for carotid endarterectomy. Journal of Vascular Surgery 2000;32(3):429‐440. Barnett, H.J.M. et al. North American Symptomatic Carotid Endarterectomy Trial (NASCET). Stroke: A Journal of Cerebral Circulation 1998;29(6)1270.
Brown, Gary C et al. The ocular ischemic syndrome. Current Opinion in Ophthalmology 1994;5(3):14‐20.
Ciftci, Suleyman et al. Intravitreal bevacizumab combined with panretinal photocoagulation in the treatment of open angle neovascular glaucoma. European Journal of Ophthalmology 2009;19(6)1028‐1033.
Eid,В TE,В etВ al.В TubeВ shuntВ surgeryВ versusneodymium:В YAGВ photocoagulationВ inВ theВ mangement ofВ neovascular glaucoma.В Opthalmology
1997;104(10):1692‐1700.
Ferguson, Gary G et al. The North American Symptomatic Carotid Endarterectomy Trial: Surgical Results in 1415 Patients. Stroke: A Journal of Cerebral Circulation 1999;30(9)1751‐1758.
Gross, Ronald. Neovascular glaucoma and ocular ischemic syndrome. Journal of Glaucoma 2000; 9:409‐412. Haymore, Jonathan G et al. Retinal vascular occlusion syndromes. International Ophthalmology Clinics 2009;49(3):63‐79. Hazin, Ribhi et al. Ocular ischemic syndrome: recent trends in medical management. Current Opinion in Ophthalmology 2009;20:430‐433. Kawaguchi, Shoichiro et al. Effect of carotid endarterectomy on chronic ocular ischemic syndrome due to internal carotid artery stenosis. Neurosurgery
2001;48(2) 328‐333. London, Nikolas et al. Update and review of central retinal vein occlusion. Current Opinion in Ophthalmology 2011;22:159‐165. Malhotra, Raman et al. Management of ocular ischaemic syndrome. British Journal of Ophthalmology 2000;84:1428‐1431. Mantese, Vito A. MD, et al. The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). Stroke 2010;41:S31‐34.
Olmos, Lisa C et al. Medical and surgical treatment of neovascular glaucoma. Int Ophthalmology Clin 2011;51(3):27‐36. Raghavan, Prashant et al. Magnetic resonance angiography of the extracranial carotid system. Topics in Magnetic Resonance Imaging 2008;19(5):241‐
249.В Saito,В YoshiakiВ etВ al.В BeneficialВ effectsВ ofВ preoperativeВ intravitreal bevacizumab onВ trabeculectomy outcomesВ inВ neovascular glaucoma.В Acta
Ophthalmologica 2010;88(1):96‐102.
Wakabayashi, Taku et al. Intravitreal bevacizumab to treat iris neovascularization and neovascular glaucoma secondary to ischemic retinal diseases in 41 consecutive cases. Ophthalmology 2008;115:1571‐1580. Winterkorn, Jacqueline M.S. et al. Recovery from ocular ischemic syndrome after treatment with verapamil. Journal of Neuro‐Ophthalmology
1995;15(4):209‐211. Wolintz, Robyn J. Carotid endarterectomy for ophthalmic manifestations: Is it ever indicated? Journal of Neuro‐Ophthalmology 2005;25(4):299‐302. Olmos, Lisa C MD, et al. Medical and Surgical Treatment of Neovascular glaucoma. Internation Ophthalmology Clinics 2011;51(3):27‐36.
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INTRODUCTION
•
VITREOUS HEMORRHAGE
Incidence: 7 cases per 100,000
•
Presenting symptoms: floaters, cloudy vision, shadows, cobwebs
•
Diagnosis: observation
•
Complete examination:
DEVELOPMENT, DIFFERENTIAL DIAGNOSIS, AND
MANAGEMENT RECOMMENDATIONS
• anterior vitreous at the slit lamp
• Indirect ophthalmoscopy with
depression
scleral
• B-scan
Marta Banh O.D.
• DFE of the contralateral eye
San Francisco VAMC Resident
• IOP*
June 23, 2013
• Gonioscopy*
• Management: dictated by underlying etiology
POSTERIOR VITREOUS DETACHMENT IN
HEALTHY ADULTS
LIQUEFACTION OF HUMAN VITREOUS
Volume of Gel and Liquid Vitreous
Vitreous Syneresis and PVD
Posterior Vitreous Detachment (PVD) is the process by which cortical vitreous gel splits
away from the internal limiting membrane (ILM) of the retina.
•
Epidemiology
• 53% in those older than age 50
• 65% in those over age 65
• 72-100% in aphakic eyes
• May occur up to 10 years early in
myopic patients
• Higher incidence in women than men
Volume of gel vitreous remains stable until about age 40, then it begins to decrease
simultaneously with the increase in liquid vitreous.
• Subsequent PVD of the fellow eye w/in
2 years of the first eye 65-88%.
Balazs EA, Denlinger JL: Aging changes in the vitreous. In: Aging and Human Visual Function, pp 45–57. New York, Alan R. Liss, 1982.
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POSTERIOR VITREOUS DETACHMENT IN
HEALTHY ADULTS
PVD development is NOT acute, but rather a slow asymptomatic process until completion.
5 Stages leading from incomplete to complete PVDs:
COMMON CAUSES OF VITREOUS HEMORRHAGE
1. Abnormal Vessels
Diabetic retinopathy (31–54%)
Neovascularization from branch/central retinal vein occlusion (4–16%)
Sickle cell retinopathy (0.2–6%)
• Stage 0: no PVD, posterior vitreous face firmly attached
to
the retina.
Retinal arteriole macroaneurysm (0.6-7%)
• Stage 1: focal perifoveal PVD: incomplete PVD localized
in the perifovea, occurring in 1-3 quadrants
Retinal tear (11–44%)
• Stage 2: incomplete, perifoveal PVD across all quadrants.
Posterior vitreous detachment without retinal tear (4–12%)
• Stage 3: detached posterior vitreous face from the retina
• Stage 4: complete PVD, detached posterior vitreous face
with Weiss ring
2. Rupture of Normal Vessels
Trauma (12–19%)
Retinal detachment (7–10%)
Terson’s syndrome (0.5–1%)
•
•
Retinal ischemia leads to VEGF release
and induces neovascularization on the
anterior retinal surface between the
posterior vitreous cortex and ILM.
•
Normal vitreous traction with eye
movement can lead to tractional forces
and rupture of these vessels .
•
Accelerated vitreous liquefaction and
syneresis is more common in diabetic
eyes even without retinopathy.
The vitreous cortex is integrally involved in
neovascularization by acting as a surface
that is necessary for the cellular
proliferation, migration, and organization of
neovascularization to occur.
Retinal Tear
30%
Vein occlusion
11%
Proliferative DR
32%
Age-related macular degeneration (0.6–4%)
Spraul CW, Grossniklaus HE. Major Review: Vitreous Hemorrhage. Surg Ophthalmol 42:3-39, 1997.
MECHANISM OF VITREOUS HEMORRHAGE
MECHANISM OF VITREOUS HEMORRHAGE
Vessels or Abnormal New Blood
Vessels
Other
13%
PVD w/o tear
8%
3. Blood From Adjacent Source
Initial Stages of Posterior Vitreous Detachment in Healthy Eyes of Older Persons Evaluated by
Optical Coherence Tomography
Arch Ophthalmol. 2001;119(10):1475-1479.
1. Bleeding From Diseased Retinal
PSR
2%
MA
2%
AMD
2%
Bleeding From Diseased Retinal Vessels or
Abnormal New Blood Vessels
•
Neovascularization may also affect the
vitreous.
- PVD occur adjacent to
neovascularization
- region of superotemporal vessels,
temporal to the macula, and adjacent to
the optic disc.
•
After partial PVD, blood may layer out
- boat shaped hemorrhage
Faulborn J, Bowald S: Microproliferations in proliferative diabetic retinopathy and their relation to the vitreous:
Corresponding light and electron microscopic studies. Graefes Arch Clin Exp Ophthalmol 223:130, 1985
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MECHANISM OF VITREOUS HEMORRHAGE
2.
Rupture of Normal Retinal Blood Vessels
•
During a PVD, vitreous traction on the retinal vasculature may compromise a blood
vessel especially at firm vitreo-retinal attachments:
•
Vitreous Base > Posterior Lens > ONH > Macula > Retinal Vessels
RESULTS
•
• Vitreous hemorrhage from a broken retinal
blood vessel, with or without a retinal tear,
occurs in 6-41% of patients with acute
symptomatic PVD.
•
24/36 eyes (67%) had at least 1 retinal break
•
11/36 eyes (31%) had more than 1 retinal break
•
88% of breaks located in the superior retina
•
14/39 eyes (39%) had RRD repaired vitrectomy & scleral buckling
•
Additional 14/39 (39%) had vitrectomy for non-clearing hemorrhage
• Vitreous hemorrhages in the setting of an
acute symptomatic PVD should alert the
doctor that the risk of a retinal breaks is 7095%.
•
Incidence of RD in eyes w/ a h/o of RD in contralateral eye was 75%
CONCLUSION
•
1-4 breaks; mean breaks 1.7
Acute, spontaneous, non-traumatic PVD with dense fundus-obscuring vitreous hemorrhage
is associated with high incidence of retinal tears and detachments,
which require prompt surgical intervention.
MECHANISM OF VITREOUS HEMORRHAGE
3. Extension of Hemorrhage Through
The Retina From Other Sources
•
All patients were examined at 6 weeks
•
Additional risk factors:patients with retinal or vitreal hemorrhage, or
pigment in the anterior vitreous (tobacco dust/shaffer’s sign) on the initial
exam were re-examined 2 weeks after initial presentation.
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
•
Extensive Subretinal hemorrhage
precedes the appearance of vitreal
blood.
•
Age-related Macular Degeneration and
Choroidal Melanoma are the two most
common underlying diseases.
•
Vitreous hemorrhage in Idiopathic
Polypoidal Choroidal Vasculopathy
(IPCV) has also been reported.
•
Ultrasonography shows a highly
echogenic subretinal mass without any
choroidal shadowing. If the
hemorrhage becomes massive, a total
hemorrhagic RD should be suspected.
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RARE COMPLICATIONS
1. Hemosiderosis Bulbi and Photoreceptor Toxicity
•
caused by iron toxicity as hemoglobin is broken down
2. Proliferative Vitreo-Retinopathy
•
336 eyes with acute spontaneous PVD
•
118 (35%) eyes had vitreous hemorrhage
•
•
•
•
macrophages and chemotactic factors induce fibrovascular proliferation
•
cell-mediated contraction of these membranes causes tangential retinal traction, fixed retinal
folds and subsequent retinal detachment
3. Ghost Cell Glaucoma
43% taking aspirin, clopidogrel, or
warfarin
31% not taking these medications
Retinal tears occurred in 46% w/ vitreous
hemorrhages versus 27% of patients w/o
vitreous hemorrhages.
•
red blood cells degenerate into smaller, khaki-colored, spherical, more-rigid cells and remain for
months following the initial hemorrhage.
•
the ghost cells enter the anterior chamber after disruption of the anterior hyaloid surface: after
accidental trauma, cataract extraction, or vitrectomy
4. Hemolytic Glaucoma
CONCLUSION: patients taking aspirin, clopidogrel, or warfarin who develop an acute PVD are more likely to
present with vitreous hemorrhage. No statistically significant association was found between the use of oral
anticoagulants in patients with acute PVD and vitreous hemorrhage and the presence of retinal
tears/detachments.
MANAGEMENT AND TREATMENT
•
Free hemoglobin, hemoglobin-laden macrophages and red-blood cell debris can block the
trabecular meshwork.
•
Clinically indistinguishable from ghost cell glaucoma
MANAGEMENT AND TREATMENT
1. Establish the etiology and source of the vitreous hemorrhage
1. Observation
• Unknown etiology and attached retina on scleral depressed exam and on
ultrasonography
• Rest with head elevated 30-45 degree angle
• Re-evaluate after 3-7 days
Observation
Referral
Referral Timing
Acute PVD w/ small VH and w/o
retinal tear on scleral depression
Acute PVD w/ VH and identified
retinal tear
Urgent
Acute PVD w/ VH and w/o retinal
tear on ultrasonography
Acute PVD w/ dense fundus
obscuring VH
Urgent
VH secondary to PDR, CRVO/BRVO Non-urgent
2. Referral to retinal specialist
VH secondary to RD, open globe
injury, AMD, and IPCV
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
Urgent
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MANAGEMENT AND TREATMENT
Timing of Vitrectomy
REFERENCES
•
Balazs EA, Denlinger JL: Aging changes in the vitreous. In: Aging and Human Visual Function, pp 45–57. New York, Alan R. Liss, 1982.
•
ETDRS report number 7. Ophthalmology 1991;98(5 Suppl):741–756.
•
Foos RY. Posterior vitreous detachment. Trans Am Acad Ophthalmol Otolaryngol. 1972;76:480-497.
Gloor BP. The vitreous. In: Moses RA, Hart MH, editors. Adler's physiology of the eye: clinical applications. St Louis: CV Mosby,
1987:246–67.
Retinal Detachment
Urgent
•
Iris or Angle
Neovascularization
Urgent
•
Le Goff MM, Bishop PN. Adult vitreous structure and postnasal changes. Eye 2008; 22: 1214-1222
•
Sarrafizadeh R, et al. Incidence of retinal detachment and visual outcome in eyes presenting with posterior vitreous separation and
dense fundus-obscuring vitreous hemorrhage. Ophthalmology 2001; 108:2273-2278.
Type 1 Diabetes
One month
•
Schweitzer KD, et al. Predicting retinal tears in posterior vitreous detachment. Can J Ophthalmol 2011; 46:481-485.
•
Sebag J, Balazx EA: Morphology and ultrastructure of human vitreous fibers. Invest Ophthalmol Vis Sci 1989;30:1871
•
Sebag J. Surgical anatomy of vitreous and the vitreoretinal interface. Duane’s Clinical Ophthalmology. 2006; Vol 6, Ch 51.
•
Sebag J. Vitreous Pathobiology. Duane’s Clinical Ophthalmology. 2006; Vol 3, Ch 39.
•
Spraul CW, Grossniklaus HE. Major Review: Vitreous hemorrhage. Surg Ophthalmol 1997 42:3-39.
•
Ruby AJ, Williams GA, Blumenkranz MS. Vitreous humor. Duane’s Clinical Ophthalmology. 2006; Ch 11.
•
Uchino E, Uemura A, Ohba N. Initial stages of posterior vitreous detachment in healthy eyes of older persons evaluated by optical
coherence tomography. Arch Ophthalmol. 2001; 119:1475-1479
•
Witmer MT, Cohen SM. Oral anticoagulation and the risk of vitreous hemorrhage and retinal tears in eyes with acute posterior vitreous
detachment. J of Retina and Vitreous Diseases.2013; 33:621-626.
Subhyaloid vitreous
hemorrhage
One month
Type 2 Diabetes
Two or three months
Other Causes
Three months or more
ETDRS report number 7. Ophthalmology 1991;98(5 Suppl):741–756.
Case PT 78 year old female
EVALВ ATВ THEВ SOCIETYВ FORВ THEВ BLINDВ (SACRAMENTO)В ONВ 1/2/2013
LV 2’ Bilateral Non-Exudative AMD
I SPY WITH MY TELESCOPIC EYE:
The Implantable Miniature Telescope for Age-Related Macular Degeneration
Caitlin E. Walsh, O.D.
University of California, Berkeley
Edwin B. Mehr Low Vision Resident
June 23, 2013
CC: Implantable Miniature Telescope Evaluation
Visual difficulties: Reading books and newspaper, writing
POHx: (-) H/o co-existing ocular disease, (-) H/o eye surgery
TF refraction
OD +1.00 -2.00 x090
OS +0.75 -1.00 x090
20/250-1
20/160+1
Contrast Sensitivity (Pelli-Robson)
5% Weber (2% Weber is normal)
Confrontation Visual Fields
(transilluminator)
Full OD and OS
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
BCVA
Anterior Segment
L/Ls
Blepharitis OU
Cornea
Clear OU
Iris
Flat OU
Lens
Gr 3+ NS OU
TA @ 10:45am 11mmHg, OS 12 mmHg
Posterior Segment
ONH
Macula
(C/D): 0.25/0.25 OU
GA OD>OS, (-)CNV OU
41
6/11/2013
Age-Related Macular Degeneration
Functional difficulties
FDA approved July 1, 2010
Consequences
Reading
Recognizing faces
Watching television
Driving
Self-care
Social interaction
The Implantable Miniature Telescope
Increased risk of accidents
More dependent on others
Decreased quality of life
Legal blindness
Depression
Indication
Monocular implant
75 years or older
Severe-profound vision loss
End-stage macular degeneration
2.7x Fixed Focus Galilean Telescope
Works in conjunction with the cornea
Optimal focal distance of 3m
Goal = Reduce the impact of the
central scotoma
IMT used for detailed tasks
Un-operated eye used for
safe travel
Projects an enlarged image of the central
field onto the retina
Field of View OUT = 20-24 degree
Field of View IN = 54 degrees
2.7x
54Вє
20Вє
http://www.nei.nih.gov/health/maculardegen/armd_facts.asp
www.centrasight.com
The Implantable Miniature Telescope
Visual effects
3.6mm (diameter) x 4.4mm (length), 13.5mm wide including haptics
Biocompatible materials
Implanted into the posterior chamber following phacoemulsification
Protrudes 0.5 mm from the pupillary plane
Prohibits binocular vision
Modifications from standard phaco with foldable IOL implantation
Retrobulbar block
12 mm limbal incision, 7 mm capsulorhexis
Prophylactic peripheral iridectomy, 10 nylon sutures
Colby
et al. 2007.
13.5В mmВ www.centrasight.com
Restricts peripheral vision
Constricted to diameter of 20 degrees
Reduced retinal illuminance
Cost = 15,500 (covered by Medicare)
4.4В mm
Visual confusion, diplopia or suppression
Loss of depth perception
Reduced contrast sensitivity
0.5В mm
4.4 mm = 13 IOLS!
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
http://www.ocutech.com/bioptic-driving.aspx
42
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Centrasight TM Treatment Program
CentrasightTM Treatment Program
A treatment program for End-Stage AMD
RetinalВ Specialist
Diagnosis, surgical evaluation, pre and postoperative care
Utilizes the Implantable Miniature Telescope
Created by Isaac Lipshitz, M.D.
Manufactured by VisionCare Ophthalmic Technologies (Saratoga, Ca)
Requires a multidisciplinary approach
Retinal specialist
Corneal and Cataract specialist
Low Vision Optometrist
Occupational Therapist
OccupationalВ Therapist
Demonstrates the External Telescope
Simulator (ETS)
Determines the patients preferred retinal locus
Determines the eye to receive the
prosthetic device
Facilitates patching exercises prior to treatment
Provides post-operative vision care
VISUAL CRITERIA
Severe to profound vision loss
BCVA (20/160 – 20/800)
Improvement in Vision with ETS
Determines good surgical candidates
Performs the surgery and post-op care
DISEASE CRITERIA
Geographic Atrophy or Disciform Scar
Bilateral foveal involvement
Provides eccentric viewing training
ANATOMICAL CRITERIA
Stable for at least 6 months
No active CNV or Tx for CNV
Baseline Endothelial Density
75-84 years old 2000 cells/mm2
85+ years old
1800 cells/mm2
Visually Significant Cataract
> or = Grade 2
Anterior chamber depth > or = 3.0mm
No co-existing ocular disease
No anterior segment
abnormalities
No condition that could
compromise
the patient’s peripheral vision
CentrasightTM Treatment Program
LowВ VisionВ Optometrist
CorneaВ andВ CataractВ Specialist
Initiates appropriate referrals
Axial length > 21 mm
Myopia < 6.0 D, Hyperopia < 4.0 D
Phakic Gr 2+ NS, CS, or PSC
Case PT 78 year old female
EVALВ ATВ THEВ SOCIETYВ FORВ THEВ BLINDВ ONВ 1/2/2013
TF refraction
OD +1.00 -2.00 x090
OS +0.75 -1.00 x090
BCVA
20/250-1
20/160+1
ETS
20/100
20/50
Provides post-operative vision rehabilitation
FUNCTIONAL CRITERIA
Realistic functional goals
IMT will not restore the patient’s
natural vision
DOES NOT eliminate need for
glasses and magnifiers
Intraocular: 5 letter improvement
Must tolerate loss of peripheral vision and
with the ETS
depth perception
Interocular: 10 letter
Must commit to working with the low vision
improvement with the ETS
optometrist and occupational therapist
compared to the other eye
following surgery
without the ETS
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
Reading Acuity using ETS over OS with +5.00D near cap
Efficiency was 0.20/2.0M (16 pt font)
Threshold was 0.20/1.25M (10 pt font
Assessment
Both eyes meet visual criteria
Target OS for IMT prosthesis
Plan
Wear eye patch over OS 2-3 hrs/day while performing tasks of daily living
Referred to the OT at the UC Davis Med Center
43
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Case GK 84 year old male
Case GK 84 year old male
EVAL AT THE SOCIETY FOR THE BLIND 1/2/2013
EVAL AT THE SOCIETY FOR THE BLIND 1/2/2013
CC: Glare and Diplopia
Pre-op Trial Frame Refraction
OD +0.75 -0.50x154
OS pl -0.25 x056
Post-op Trial Frame Refraction
OD +3.25 -1.50 x060
OS +0.50 -0.50 x045
BCVA
20/400
20/500
ETS
20/100
BCVA
20/125
20/200
Reading acuity with a +5.00 D Add
Efficiency
Threshold
0.2/2.5M
0.2/1.6M
Contrast Sensitivity (Pelli-Robson)
OD 36% Weber and OS 6.3% Weber
Assessment
Good improvement in visual acuity with IMT OD
Light sensitivity
Reduced suppression of eye with IMT prosthesis
Plan
Released SV Distance SRx and SV Near SRx
Recommended gray Cocoon fit-overs
Recommended continued training with the occupational therapist to work
on alternating fixation
Confrontation Visual Fields
Severely constricted <20 degrees 360 OD
No restriction OS
Conclusions
Conclusions
GOOD CANDIDATES FOR THE IMT
POOR CANDIDATES FOR THE IMT
• Meet anatomical and disease criteria
• Previous intraocular surgery
• Improvement in visual acuity with the external telescope simulator
• Anterior segment abnormalities
• Realistic goals and expectations
• Constricted peripheral vision in un-operated eye
• Willing to work with rehabilitation specialists
• Prone to eye rubbing
• Good chance of useful improvement in everyday activities
• Cognitive impairment
• Good chance of adjusting to change in vision
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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Conclusions
Acknowledgments
Careful patient evaluation, education, and selection are
essential for a happy patient following surgery!
Society for the Blind
Richard Van Buskirk, O.D.
Nancy Nguyen, O.D.
Penny Riley, Clinic Coordinator
IMT will not restore natural vision
Glasses and magnifiers will still be necessary following surgery
UC Berkeley School of Optometry
Robert B. Greer, O.D.
Marlena Chu, O.D.
Ian Bailey, O.D.
Cheyenne Huber, O.D.
UC Davis Medical Center
Time and effort required for post-surgical visual rehabilitation
Jennifer Li, M.D.
Mark Mannis, M.D.
Terri Hayward, O.T.
Colby et. al. 2007.
Resources
•
•
•
•
•
•
•
•
•
•
•
•
Brown, M. et al. Utility values associated with blindness in an adult population. Br J
Ophthalmol2001;85:327-331.
CATT Research Group, Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL, Jaffe GJ. N Engl J Med.
2011 May 19; 364(20):1897-908.
Colby KA et al. Surgical Placement of an optical prosthetic device for end-stage macular
degeneration: the implantable miniature telescope. Arch Ophthalmol. 2007;125:1118-1112.
Colucciello, M. The Merits and Limitations of the Implantable Miniature Telescope for AMD. Retinal
Physician. 2010. http://www.retinalphysician.com/articleviewer.aspx?articleid=104846. Accessed April
28, 2013.
FDA approval letter for Implantable Miniature Telescope. Food & Drug Administration Web Site.
http://www.accessdata.fda.gov/cdrh_docs/pdf5/P050034a.pdf. Accessed February 18, 2013.
Garfinkel, RA, Berinstein, DM, Frantz, BS. Treatment of Choroidal Neovascularization Through the
Implantable Miniature Telescope. Am J Ophthalmol. 2006;141: 766-767.
Haddrill, M. FDA-Approved Macular Degeneration Treatment.
<Http://www.allaboutvision.com/conditions/amd-treatments.htm>.
Haller, JA. A New Option for End-Stage AMD. Review of Ophthalmology. 2010.
http://www.revophth.com/content/d/retinal_insider/c/25844/
Harvitt, DM. Lecture 1. Vision Science 203B. Spring 2013.
Hudson et al. IMT-002 Study Group. Implantable miniature telescope for the treatment of visual
acuity lossresulting from end-stage age-related maculard egeneration: 1 year results. Ophthalmology.
2006;113:1987-2001.
Hudson et al. Implantable Telescope for End-stage Macular Degeneration: Long term Visual Acuity
and Safety Outcomes. J Ophthalmol 2008;146:664–673.
Lane. SS, Kuppermann, BD. The implantable miniature telescope for macular degeneration. Curr Opin
Ophthalmol. 2006;17(1):94-98.
Resources
•
•
•
•
•
•
•
•
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
Lane, SS et al. A prospective multicenter clinical trial to evaluate the safety and
effectiveness of the implantable miniature telescope. Am J Ophthalmol. 2004; 137:9931001.
Rein, DB, Wittenborn, JS, Zhang, X, Honeycutt, AA, Lesesne, SB, Saaddine, J,.
Forecasting Age-Related Macular Degeneration Through the Year 2050: The Potential
Impact of New Treatments. Arch Ophthalmol. 2009;127 (4): 533-540.
Rosner, M, Ben-Simon, G, Sachs, D. Feasibility and Safety of Laser Treatments in eyes
with an Intraocular Implantable Miniature Telescope. J Cataract and Refractive
Surgery.2003; 29:1005-1010.
Singer, M et al. Pars plana posterior capsulotomy in a patient with a telescope prothesis
for age-related macular degeneration. Arch Ophthalmol. 2010;128(8):1065-1067.
VisionCare’s Implantable Miniature Telescope: An intraocular telescope for treating
severe to profound vision impairment due to bilateral end-stage age-related macular
degeneration. Patient Information Booklet. Saratoga: VisionCare Ophthalmic
Technologies, Inc, 2010. Print.
VisionCare’s Implantable Miniature Telescope: An intraocular telescope for treating
severe to profound vision impairment due to bilateral end-stage age-related macular
degeneration. Professional Use Information. Saratoga: VisionCare Ophthalmic
Technologies, Inc, 2010. Print.
Williams, R, Brody, BL, Thomas, RG, Kaplan, RM, Brown, SI. The Psychosocial Impact of
Macular Degeneration. Arch Ophthalmol. 1998;116:514-520.
Ying, GS, Maguire, M. Development of a Risk Score for Geographic Atrophy in
Complications of the Age-Related Macular Degeneration Prevention Trial. Ophthalmology
2011;118:332–338.
45
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Keratoglobus
PKP after KCN: the thick and
thin of it
Tarah Lee, OD
VA Palo Alto Health Care System
Primary Care and Low Vision Rehabilitation Resident
Cirrus anterior segment OCT
PentacamВ images
OD
http://www.kerasoftic.com/en/eye‐care‐professional/educational/
OS
http://benjamineye.com/sites/benjamineye.com/files/i
mages/page/pentacam_hr_overview_display.jpg
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
46
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PKP Procedure
Indications for PKP
• Anterior Cornea
– Keratoconus (KCN)
– Corneal Dystrophies
– Trauma – chemical burns
– Infections – scars
– Stevens-Johnson Syndrome (SJS)
– Ocular cicatricial pemphigoid (OCP)
Hong Kong Med J. 2012 Dec;18(6):509‐16.
Indications for PKP con’t
Indications for PK
• Posterior Cornea
– Fuchs endothelial dystrophy
– Bullous Keratopathy
• Aphakic (ABK)
• Pseudophakic (PBK)
– Posterior polymorphous dystrophy (PPMD)
– Corneal regraft
http://openi.nlm.nih.gov/detailedresult.php?img=2880372_MEAJO‐17‐38‐g002&req=4
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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PKP in KCN
Early complications of PKP
Suture problems
Macular edema
Primary graft failure
Elevated IOP
Wound leaks
Persistent epithelial defects
Filamentary keratopathy
Choroidal hemorrhage
Retinal detachment
Hyphema
Microbial keratitis
Endophthalmitis
• Immunological rejection rare
•
•
•
•
•
•
•
•
•
•
•
•
Late complications of PKP
Lamellar Keratoplasty
• 10-20% of patients
• Good visual outcomes
•
•
•
•
•
•
•
Late endothelial failure
Unstable refractive endpoint
Cataracts
Glaucoma
Graft rejection
Epithelial downgrowth
Transmission of infectious diseases
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
HostВ Tissue
DonorВ Tissue
PLK
SuperiorВ scleral pocket
Posterior stroma,В DMВ andВ endo
DLEK
Posterior cornealВ disc
Posterior stroma,В DMВ andВ endo
DSEK
Endothelium and Descement’s
membraneВ strippedВ PosteriorВ stroma, DMВ andВ endo
DSAEK
Endothelium and Descement’s
membraneВ stripped
PosteriorВ stroma, DMВ andВ endothelium
DMEK
Descemet’s membrane and endothelium stripped
DMВ andВ endothelium
DALK
DMВ andВ endothelium
Epithelium to deepВ stroma
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Advantages and disadvantages of
DALK vs. PKP
DALK
Advantages
Disadvantages
Eliminates riskВ ofВ endothelialВ rejection MoreВ technicallyВ demanding
ReducedВ endothelialВ cellВ loss
ProlongedВ operativeВ time
AnticipatedВ improvedВ graftВ survival
AstigmatismВ ratesВ similar toВ PKP
LargelyВ extraocular procedure
RiskВ ofВ conversionВ toВ PKP
GreaterВ woundВ strength
DoubleВ A/C,В interface haze
LessВ dependenceВ onВ topicalВ steroids
RecurrenceВ ofВ stromal cornealВ dystrophies
EarlierВ sutureВ removal
ContraindicatedВ ifВ stroma tooВ thinВ orВ excessiveВ DMВ striae
Similar refractiveВ errorВ andВ BCVA
http://www.revoptom.com/continuing_education/tabviewtest/lessonid/107933/
Corneal Collagen
Cross-linking (CXL)
Intracorneal Ring Segments (ICRS)
• May slow progression of
• PMMA segments
KCN
• May include epithelial
http://www.shinagawa.com.sg/en/lasik-services/lasik-xtra
• Flatten and reshape the
debridement
• Topical riboflavin
• Implanted into stroma
370 um
http://www.coastalvisionmedical.com/site/intacs.htm
cornea
• UV-A exposure at 370 um
http://www.oocities.org/wallstreet/2124/KERAweb/CornealChange
s.html
http://www.revophth.com/content/i/1777/c/32329/
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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Key Points
References
•
• Penetrating keratoplasty (PKP) has been the mainstay
of surgical treatment for corneal blindness
• Many potential complications, though most are rare
• Allograft rejection and late endothelial failure are the
most common causes of graft failure
• Regrafts are 3x as likely to fail as primary grafts
• Increase in lamellar corneal transplants due to
improved surgical techniques
• Alternative treatments such as intracorneal ring
segments and corneal collagen cross-linking are
available
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Young AL, Kam KW, Jhanji V, Cheng LL, Rao SK. A new era in corneal transplantation: paradigm shift and evolution of
techniques. Hong Kong Med J. 2012 Dec;18(6):509-16.
Wang J, Hasenfus A, Schirra F, Bohle RM, Seitz B, SzentmГЎry N. Changing indications for penetrating keratoplasty in
Homburg/Saar from 2001 to 2010--histopathology of 1,200 corneal buttons. Graefes Arch Clin Exp Ophthalmol. 2013
Mar;251(3):797-802.
Stechschulte SU, Azar DT. Complications after penetrating keratoplasty. Int Ophthalmol Clin. 2000 Winter;40(1):27-43.
Chan E, Snibson GR. Current status of corneal collagen cross-linking for keratoconus: a review. Clin Exp Optom. 2013
Mar;96(2):155-64
Jhanji V, Sharma N, Vajpayee RB. Management of keratoconus: current scenario. Br J Ophthalmol. 2011 Aug;95(8):104450.
Cassidy D, Beltz J, Jhanji V, Loughnan MS. Recent advances in corneal transplantation for keratoconus. Clin Exp Optom.
2013 Mar;96(2):165-72.
Reinhart WJ, Musch DC, Jacobs DS, Lee WB, Kaufman SC, Shtein RM. Deep anterior lamellar keratoplasty as an
alternative to penetrating keratoplasty a report by the american academy of ophthalmology. Ophthalmology. 2011
Jan;118(1):209-18.
Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998 Jan-Feb;42(4):297-319
Romero-JimГ©nez M, Santodomingo-Rubido J, Wolffsohn JS. Keratoconus: a review. Cont Lens Anterior Eye. 2010
Aug;33(4):157-66;.
Tan DT, Dart JK, Holland EJ, Kinoshita S. Corneal transplantation. Lancet. 2012 May 5;379(9827):1749-61.
Borderie VM, Sandali O, Bullet J, Gaujoux T, Touzeau O, Laroche L. Long-term results of deep anterior lamellar versus
penetrating keratoplasty. Ophthalmology. 2012 Feb;119(2):249-55.
Fares U, Sarhan AR, Dua HS. Management of post-keratoplasty astigmatism. J Cataract Refract Surg. 2012
Nov;38(11):2029-39.
Tan DT, Por YM. Current treatment options for corneal ectasia. Curr Opin Ophthalmol. 2007 Jul;18(4):284-9.
Claesson M, Armitage WJ. Clinical Outcome of Repeat Penetrating Keratoplasty. Cornea. 2013 Apr 12.
Collagen-Crosslinking: asking the tough questions. Retrieved June 1, 2013.
http://www.revophth.com/content/i/1777/c/32329/
CXL USA online. Retrieved June 1, 2013. http://www.cxlusa.com/default.aspx
Ertan A, Muftuoglu O. Intracorneal ring segments for keratoconus. Expert Rev Ophthalmol. 2008;3(5):585-591.
Chief Complaint: 81 year‐old male with painful red eye OS
Scleritis:В AВ RoyalВ PainВ inВ theВ Eye
JenniferВ M.В Tu,В OD
SanВ FranciscoВ VAВ MedicalВ Center
PrimaryВ Care
ExamВ Findings
Right Eye
VA cc
20/40
20/40
Lids/Lashes
Collarettes 2+
Collarettes 2+,В mucousВ 2+В LL
Conjunctiva/Sclera
Clear
Injection 4+, small elevated nodule @sup‐temp under lid
Cornea
TraceВ KP
TraceВ KP
AntВ Chamber
DeepВ andВ quiet
DeepВ andВ quiet
16В mm Hg
IOP
16В mm Hg
Lens
NSВ 2+
NSВ 2+
Vitreous
Syneresis
Syneresis
OpticВ Nerve:В JuneВ 23,В 2013
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
LeftВ Eye
Macula:
Periphery:
OD:В 0.30
OS:В 0.35
A:В NodularВ anteriorВ scleritis OS
ScatteredВ smallВ drusen 1+В OU,В noВ CNV
P:В BeginВ ibuprofenВ 400В mgВ QID.
NoВ holes/tears/breaksВ OU
B‐scan:
Negative T‐sign
Order lab tests (CBC, ESR, PPD, RPR, TP‐PA, ANA, ACE, ANCA, RF)  50
6/11/2013
Anatomy
DifferentialВ Diagnosis
• Conjunctivitis
• Acute angle closure
– Diffuse redness
– Teary eyes, mucous discharge
– Papillary vs follicular reaction
– Elevated IOP with acute eye pain
– Mid‐dilated pupil
– CornealВ edemaВ пѓ hazyВ vision
Episcleritis
• Anterior uveitis*
–
–
–
–
PainВ withВ photophobia
Circumlimbal flush
Keratic precipitates
AnteriorВ chamberВ reaction
Younger
Older
Onset
Acute
Insidious
VA
Unaffected
ReducedВ VA
Blood
Vessels
Sectoral superficial
injectionВ (brightВ red)
Superficial andВ deepВ vesselВ injectionВ (violaceous hue)
Vessels blanchВ withВ phenylephrine
DeepВ vessels doВ notВ blanchВ withВ phenylephrine
No pain
Severe,В deep, boring
Pain
BloodВ Supply
•
•
DerivedВ fromВ theВ anteriorВ ciliary arteriesВ whichВ anastamose
withВ theВ posteriorВ ciliary arteries
TheВ scleraВ itselfВ isВ anВ avascularВ structure
1. Conjunctival Plexus
• Mobile with a cotton tip
2. SuperficialВ Episcleral Plexus
ComposedВ ofВ collagen,В fibroblasts,В andВ GAGs
Extraocular musclesВ insertВ intoВ theВ sclera
InnervationВ byВ longВ andВ shortВ ciliary nerves
BloodВ supplyВ derivedВ fromВ theВ anteriorВ ciliary arteries
Scleritis
Age
*MayВ presentВ withВ scleritis
•
•
•
•
Conjunctiva
Sclera
Tenon’s space
Episclera
PathophysiologyВ ofВ Scleritis
• Histology studies show granulomatous lesion consisting of plasma cells, lymphocytes, and mast cells clinically manifesting as scleral inflammation
Active T‐cell inflammatory response  incited by trauma or infection
EndothelialВ swellingВ ofВ vesselsВ andВ microvascular
occlusion
SCLERALВ INFLAMMATION
• Radial orientation of vessels
3. DeepВ Episcleral Plexus
• Do not blanch with phenylephrine
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
CollagenВ fibrilsВ unravelВ dueВ toВ alterationВ ofВ proteoglycans
NeutrophilВ infiltrationВ ofВ vesselВ wall
51
6/11/2013
ClinicalВ ExaminationВ Checklist
History
ExternalВ Exam
Pain
OnsetВ (acuteВ vs insidious)
EvaluateВ inВ naturalВ lighting
Violaceous vs brightВ redВ hue
Slit LampВ Exam
Red freeВ filter
CornealВ complications
‐ Marginal or interstitial keratitis
Anterior chamberВ cellВ Posterior Segment
Exudative retinalВ detachment
B scan for fluid under Tenon’s capsule (T‐sign)
ClassificationВ Types
Diffuse
Nodular
Scleromalacia
Perforans
(NecrotizingВ withoutВ inflammation)
NecrotizingВ withВ inflammation
Anterior
Posterior
Scleritis
Note:В useВ anВ opticВ sectionВ toВ determineВ extentВ ofВ edemaВ andВ whichВ layersВ areВ involved
Diffuse AnteriorВ Scleritis
• Seen in 60% of cases
• Rearrangement of collagen scleral fibers – resulting in blue hue
• Systemic association in 45% of cases
– Rheumatoid arthritis most common
• Corneal findings
– Peripheral infiltrates
– Corneal thinning
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
NodularВ AnteriorВ Scleritis
• Seen in 20% of cases
• May have multiple nodules present
• Systemic association in 40 – 50% of cases
–
CommonlyВ infectiousВ origin
• Underlying sclera may be transparent however no necrosis
Firm,В immobile,В tenderВ nodule
typicallyВ foundВ closeВ toВ limbus
52
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Scleromalacia perforans
NecrotizingВ withВ inflammation
PosteriorВ Scleritis
(NecrotizingВ withoutВ inflammation)
•
•
•
•
LackВ ofВ symptoms
SevereВ atrophyВ ofВ theВ episclera
Yellow‐white infarcted tissue
AssociatedВ withВ longstandingВ RA
• White sclera due to capillary dropout
• Infarction and necrosis of underlying sclera
• Scleral edema extending outward around the globe (pictured below)
• Inflammation occurs posterior to medial and lateral rectus muscle insertions
• Less commonly associated with systemic disorders
• Ocular complications
• Uveitis
• Retinal detachment
• Proptosis and diplopia
• Subretinal mass
• Choroidal effusion
OcularВ ComplicationsВ definedВ asВ theВ following:
• Interstitial keratitis
• Cataract
• Marginal corneal ulcer
• Vitritis
• Anterior uveitis
• Cystoid macular edema
• IOP > 21 mm Hg
• Exudative retinal detachment
DecreasedВ Vision
78% had pre‐existing systemic  diagnosis
OfВ 243В patients
44%В ofВ patientsВ haveВ anВ associatedВ systemicВ condition
PosteriorВ SegmentВ Findings
14%В diagnosedВ afterВ initialВ evaluation
• None in episcleritis group
• 16% in scleritis group
InfectiousВ (7%)
ConversionВ toВ BilateralВ Disease
T‐sign = thickened sclera with fluid in Tenon’s space
• Episcleritis: • Scleritis: Rheumatic (37%)
8%В diagnosedВ duringВ followВ upВ period
12%В atВ 1В year
24%В atВ 1В year
• Commonly seen in posterior scleritis
• Infrequently associated with anterior scleritis
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
HerpesВ zosterВ (4.5%)
RheumatoidВ arthritisВ (15.2%)
Wegener’s Granulomatosis (+systemic vasculitides)
SystemicВ lupusВ erythematosus
53
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LaboratoryВ Testing
CompleteВ bloodВ countВ (CBC)
CompleteВ metabolicВ panelВ (CMP)
Antineutrophil cytoplasmic antibody (C‐ANCA and P‐ANCA)
AntinuclearВ antibodyВ (ANA)
AngiotensinВ convertingВ enzyme
Fluorescent treponemal antibody absorption (FTA‐Abs)
RapidВ plasmaВ reagin (RPR)
RheumatoidВ factorВ (RF)
PurifiedВ proteinВ derivativeВ (PPD)
LymeВ antibody
Lysozyme
Chest x‐ray
TakeВ HomeВ Points
TreatmentВ Options
NSAID
OralВ corticosteroids
ImmunosuppressiveВ drugs
Initial drug of choice for non‐
necrotizingВ anteriorВ scleritis
InitialВ drugВ ofВ choiceВ forВ necrotizingВ anteriorВ scleritis
andВ posteriorВ scleritis
OR
FailedВ NSAIDВ therapy
NecrotizingВ anteriorВ scleritis
OR
FailedВ corticosteroidВ therapy
OR
SteroidВ relatedВ adverseВ events
References
1. Akpek EK, Thorne JE, Qazi FA, Do DV, Jabs DA. Evaluation of patients with scleritis for systemic disease. Ophthalmology. 2004 Mar;111(3):501‐6. 2. Beardsley RM, Suhler EB, Rosenbaum JT, Lin P. Pharmacotherapy of scleritis: current paradigms and future directions. Expert Opin Pharmacother. 2013 Mar;14(4):411‐24. • Be able to recognize the clinical features in differentiating episcleritis from scleritis
3. Castells DD. Anterior scleritis: three case reports and a review of the literature. Optometry. 2004 Jul;75(7):430‐44. 4. Galor A, Thorne JE. Scleritis and peripheral ulcerative keratitis. Rheum Dis Clin North Am. 2007 Nov;33(4):835‐54, vii.
5. Nizam S, Johnstone A, Green M, Gough A. Necrotising scleritis and connective tissue disease‐‐three cases and a review. Clin Rheumatol. 2009 Mar;28(3):339‐41. • Scleritis is a severe ocular inflammatory disorder that may have systemic disease implications
6. Jabs DA, Mudun A, Dunn JP, Marsh MJ. Episcleritis and scleritis: clinical features and treatment results. Am J Ophthalmol. 2000 Oct;130(4):469‐76.
7. Jachens AW, Chu DS. Retrospective review of methotrexate therapy in the treatment of chronic, noninfectious, nonnecrotizing scleritis. Am J Ophthalmol. 2008 Mar;145(3):487‐492. 8. Raiji VR, Palestine AG, Parver DL. Scleritis and systemic disease association in a community‐based referral practice. Am J Ophthalmol. 2009 Dec;148(6):946‐50.
• Urgent referral is warranted to initiate laboratory testing and possible systemic treatment of the underlying condition
9. Sainz de la Maza M, Molina N, Gonzalez‐Gonzalez LA, Doctor PP, Tauber J, Foster CS. Clinical characteristics of a large cohort of patients with scleritis and episcleritis. Ophthalmology. 2012 Jan;119(1):43‐50. 10. Sainz de la Maza M, Molina N, Gonzalez‐Gonzalez LA, Doctor PP, Tauber J, Foster CS. Scleritis therapy. Ophthalmology. 2012 Jan;119(1):51‐8. 11. Watson PG, Hayreh SS. Scleritis and episcleritis. Br J Ophthalmol. 1976 Mar;60(3):163‐91.
12. Wieringa WG, Wieringa JE, ten Dam‐van Loon NH, Los LI. Visual outcome, treatment results, and prognostic factors in patients with scleritis. Ophthalmology. 2013 Feb;120(2):379‐86. doi: 10.1016/j.ophtha.2012.08.005. Epub 2012 Nov 20. PubMed PMID: 23177360. UC BERKELEY RESIDENT FORUM JUNE 2013
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NotВ AlwaysВ onВ Target
TICKEDВ OFFВ PATIENTS
OcularВ ManifestationsВ ofВ LymeВ Disease
SeveralВ countries
43В States
CaliforniaВ isВ consideredВ anВ endemicВ area
http://www.pbase.com/image/51179027
RyanВ Johnson,В OD
Resident,В BinocularВ VisionВ Clinic
UniversityВ ofВ California,В Berkeley
JuneВ 23,В 2013
Pathognomoic
SeenВ inВ 50%В ofВ patients
AtВ riskВ afterВ 24В hours
http://hardinmd.lib.uiowa.edu/cdc/lymedisease6.html
• Between 3 & 30 days
• No later than 3 months
• Erythema Migrans
• Borrelial lymphocytoma
• 6 months
• Migrant muscle pain
• Large joint pain
• Bone pain
100%В transmissionВ byВ 3В days
CDCВ DefinitionВ ofВ LymeВ Disease
• Exposure in an endemic area
• Erythema migrans within 30 days
Dermatologic
Musculoskeletal
AВ MultisystemВ Disorder
•
•
•
•
ExposureВ inВ anВ endemicВ area
Erythema migrans absent
SignsВ involvingВ oneВ organВ system
PositiveВ laboratoryВ test
• Within several weeks
• 4‐8% of patients
• Atrioventricular blocks
• Carditis
• Highly variable
• Months to years after
• Bannwarth Syndrome
• Encephalomyelitis
• Cranial nerve palsies
• No history of exposure
• Erythema migrans present
• Involvement of two organ systems
Cardiac
Neurologic
• No exposure in an endemic area
• Erythema migrans present
• Positive serology
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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DocumentedВ ManifestationsВ ofВ Lyme
RoughВ andВ Ready,В California:В 12yo
•
•
•
•
•
•
•
•
•
•
•
•
•
Blepharospasm
Uveitis
Panophthalmitis
Chorioiditis
Optic Disc Edema
Macular Edema
Pseudotumor
Cerebri
Optic Neuritis
AION
Temporal Arteritis
Optic Atrophy
Horner’s
Syndrome
Argyll-Robertson
Pupil
STAGEВ 3:В Late/Immunologic
• Conjunctivitis
• Periorbital Edema
STAGEВ 2:В Dissemination
STAGEВ 1:В Infection
• Diagnosed with active neuro‐lyme disease 2011
•
•
•
•
•
•
Nerve Palsies
Stromal Keratitis
Episcleritis
Scleritis
Orbital Myositis
Cortical Blindness
– Confirmed with ELISA and Western Blot
– Presumed contracted at 6yo (2007)
• Lyme‐associated arthritis in both knees
• Presenting Complaints:
–
–
–
–
Photophobia
Floaters
MidlineВ Shift
TrackingВ Difficulties
MechanismsВ ofВ TBIВ andВ VisualВ ConsequencesВ inВ MilitaryВ andВ VeteranВ Populations
OptometryВ &В VisionВ Science
FebruaryВ 2013
• 65% ‐ Reported visual problems
• 50% ‐ Reading problems
• Light Sensitivity
– 67% of blast related
– 33% of non‐blast related
• Convergence insufficiency
• Accommodative dysfunction
• Oculomotor anomalies
• Ocular Inflammation
– Keratitis
– Anterior Uveitis
– Intermediate Uveitis
http://directorsblog.health.azdhs.gov/?p=3493
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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PerceptualВ Difficulties
OcularВ Motility
SanВ Jose,В California:В 19yo
• Diagnosed in 2011
• Smooth Pursuits & Integration
• Fast & Accurate Saccades
• No Midline Hesitation
– No associated tick bite
– Presumed contracted at 15yo (2010)
– Stage 3
DEM
• Difficulties with Rapid Automatic Naming
• Adequate Spatial Planning and Tracking Skills
PMA‐PS
• Presenting Complaints:
– Diplopia; Intermittent at distance
– “Jerky Tracking”
– Intermittent blurry vision
• Reduced Visual Processing Speed
TVAS
• Spatial Planning Difficulties
CranialВ NerveВ Literature
CranialВ NerveВ 6В Palsy
• Lacomte ‐ 1989
• Esophoria; DI
• Increases in lateral gaze
• OS: Abduction restriction
OcularВ Posture
OcularВ Motility
п‚—
п‚—
AbducensВ palsy
п‚—
ParalyticВ sixthВ nerveВ palsy
в—¦ MostВ commonВ causeВ ofВ diplopia
п‚—
SymptomaticВ forВ 10В years
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
в—¦ Diplopia
AbsenceВ ofВ adductionВ restrictionВ 2В weekВ treatmentВ protocolВ в—¦ 200mgВ doxycyclineВ perВ day
• Divergence difficulties
FacialВ palsyВ mostВ common
MRIВ showedВ inflammationВ of:
Bilateral:В CNВ 3,7,9,10,11,12
Unilateral:В 4,5,6
Collegium Antropologicum
2005 ‐ Zrinsnak
в—¦ RulesВ outВ nuclearВ lesion
Vergence
• Diplopia during binocular facility
–
–
–
–
ClinicalВ InfectiousВ Disease
2009 ‐ Sauer
п‚—
Accommodation
• Van Erp ‐ 2011
– Facial palsy most common
• 2/3 unilateral, 1/3 bilateral
– Usually during second month of disease
– Oculo‐motor nerve also described
or
в—¦ Headaches
п‚—
StrabismusВ surgery
в—¦ InitialВ 40pDВ esotropia
◦ Post‐Op: 10pD esotropia
в—¦ 2gВ ceftriaxoneВ perВ day
в—¦ UnableВ toВ abduct
п‚—
Resolution at 2 ‐12 weeks
в—¦ DiplopiaВ remained
п‚—
ResolutionВ throughВ 7В years
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Tuolumne,В California:В 29yo
DiagnosingВ ConvergenceВ Palsy
• Diagnosed in 2010
• Diplopia
• jj
– When watching TV or reading
– Horizontal
– 6 months
• Arthritis
• “Brain fog”
– Changes in memory
– Clumsy
– Changes in cognitive functioning
• Versions
• Ductions
OcularВ Motility
OcularВ Posture
• R‐AX(T)
• Divergence
• Convergence
• NPC
Vergence
• Headaches
SeeingВ ThroughВ TheВ BrainВ Fog
DEM
PMA‐PS
• Difficulties with Rapid Automatic Naming
• Adequate Spatial Planning and Tracking Skills
• Reduced Visual Processing Speed
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
Readalyzer
• Increased Number of Fixations
• Prolonged Fixation Duration
• Reduced Reading Rate
DenaliВ NationalВ Park,В Alaska:В 37yo
• Diagnosed with Lyme disease in 2012
• Suspected present for more than 10 years
• Presenting Complaints:
– Asthenopia & fatigue with reading
– Auditory processing easier than visual processing 58
6/11/2013
LymeВ DiseaseВ asВ anВ AcquiredВ BrainВ Injury
PerceptualВ Difficulties
OcularВ Motility
DEM
VariabilityВ ofВ Presentation
LightВ Sensitivity
п‚— ConvergenceВ InsufficiencyВ &В Palsy
п‚— CranialВ NerveВ Palsies
п‚— VisualВ PerceptualВ Difficulties
п‚—
п‚—
• Pursuits: Saccadic Intrusions
• Saccades: Hypometric
• Difficulties with Rapid Automatic Naming
• Adequate Spatial Planning and Tracking Skills
References
•
•
•
PMA‐PS
• Reduced Visual Processing Speed
•
•
•
•
Readalyzer
• Increased Number of Fixations
• Prolonged Fixation Duration
• Reduced Reading Rate
•
•
•
•
•
Biesiada, Grazyna et al. “Lyme Disease: Review.” Archives of Medical Science. 6 (2012): 978‐82.
Fatterpekar, Girish et al.  “Orbital Lyme Disease: MR Imaging Before and After Treatment: Case Report.” American Journal of Neuroradiology. 23 (2002): 657‐9.
Goodrich, GL et al.  “Mechanisms of TBI and Visual Consequences in Military and Veteran Populations.” Optometry & Visual Science. 90.2 (2013): 105‐12.
Huppertz, Hans‐Iko et al.  “Ocular Manifestations in Children and Adolescents With Lyme Arthritis.” British Journal Ophthalmology. 83.11 (1999): 1149‐52.
Lecomte, F et al.  “Neurological Maifestations of Lyme Disease and Treatments.” Biomedical and Pharmacotherapy. 43 (1989): 409‐413.
Mikkila, Helena et al.  “The Expanding Clinical Spectrum of Ocular Lyme Borreliosis.” Ophthalmology. 107.3 (2000): 581‐87.
Mora, Paolo and Carta, Arturo.  “Ocular Manifestations of Lyme Borreliosis in Europe.” International Journal of Medical Sciences. 6.3 (2009): 124‐
125.
Sauer, Arneud et al. “Five Cases of Paralytic Strabismus as a Rare Feature of Lyme Disease.” Clinical Infectious Diseases. 48 (2009): 756‐9.
Sperling, J et al.  “Evolving Perspectives on Lyme Borreliosis in Canada.” The Open Neurology Journal. 6 (2012): 94‐103.
Van Erp, Willemijn et al.  “Opsoclonus and Multiple Cranial Neuropathy as a Manifestation of Neuroborreliosis.” Neurology. 77 (2011): 1013‐14.
Winterkorn, Jacqueline.  “Lyme Disease: Neurologic and Ophthalmic Manifestations.” Survey of Ophthalmology. 35.3 (1990): 191‐204.
Zrinsnak, Ognjen et al.  “Paralytic Strabismus as a Manifestation of Lyme Borreliosis. Coll Anthropology. 29 (2005): 137‐9.
NothingВ butВ Net:
ChoroidalВ NeovascularВ MembranesВ forВ theВ PrimaryВ CareВ Optometrist
JillianВ F.В Meadows,В OD,В MS
SanВ FranciscoВ VAMC
JuneВ 23,В 2013
RFV:
temporally associated with getting “dust in eye” while driving two days ago
OcularВ Hx:
VAsc (cPH)
MRx
Pupils
AntВ Seg Health
Ta (Tonosafe)
ONH
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
CaseВ Presentation
63 y/o HMВ presentedВ withВ decreasedВ visionВ OD,В CE/PCIOL 1999В OU
OD
OS
20/150‐ (NI)
20/30+ (20/20)
NI
‐‐
ERRL, (‐)APD
ERRL, (‐)APD
WNL
WNL
16
16
0.35,В fullВ pinkВ rim
0.35,В fullВ pinkВ rim
Macula
SeeВ photo
Flat,В clear
Post Seg Health
SeeВ photo
1 intraretinal flameВ hemorrhage,В roundВ hypopigmented areaВ nasalВ toВ foveaВ В 59
6/11/2013
CaseВ Presentation
CaseВ Presentation
PresumedВ idiopathicВ choroidalВ neovascularВ membrane
CardinalВ SignsВ ofВ CNV
PigmentВ epithelialВ detachment
CardinalВ SignsВ ofВ CNV
CystoidВ macularВ edema
SubretinalВ fluid
IrregularВ elevationВ ofВ RPE
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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CardinalВ SignsВ ofВ CNV
SubretinalВ andВ intraretinal
LipidВ exudation
DifferentialВ DiagnosisВ ofВ CNVM
hemorrhage
Idiopathic
ExudativeВ AMD
ExcessiveВ photocoagulation
ChoroidalВ rupture
Polypoidal
CNVM
ChoroidalВ tumors
MacularВ Telangiectasia
PathologicВ myopia
NormalВ VasculatureВ Development
AllВ organsВ exceptВ theВ brainВ andВ kidneyВ areВ vascularizedВ viaВ vasculogenesis.
Angioid
streaks
CSCR
POHS
EmbryologicВ VasculatureВ Development
Vasculogenesis
Angiogenesis
Vasculogenesis:В LocalВ precursorВ cellsВ differentiate intoВ endothelialВ cells,В whichВ subsequentlyВ joinВ toВ formВ vessels
Angiogenesis:В Blood vesselsВ sproutВ fromВ existingВ vesselsВ andВ penetrateВ adjacentВ tissue
TheВ retinaВ isВ vascularizedВ byВ bothВ vasculogenesis andВ angiogenesis.
HighlyВ coordinatedВ processВ involvingВ VEGF,В itsВ receptors,В andВ otherВ growthВ factors
Final “maturation” process allows vessels to recruit pericyte support and develop structural integrity, facilitated by PDGF, Ang1, Ang2, TGF‐β1.
Copyright В© 2001, European Society of Cardiology
Conway E M et al. Cardiovasc Res 2001;49:507-521
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
AllВ mediatedВ byВ VEGFВ (andВ friends)
61
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VEGFВ andВ Whom?
VascularВ EndothelialВ GrowthВ FactorВ Family
• Glycoproteins • VEGF‐A, ‐B, ‐C, ‐D, ‐E
• Placental Growth Factor (PlGF)
PathologicВ VasculatureВ Development
UnregulatedВ angiogenesisВ thatВ lacksВ maturationВ intoВ vesselВ competency,В resultingВ inВ leakyВ vesselsВ ofВ poorВ integrity
ProducedВ byВ RPE,В MГјllerВ cells,В pericytes,В endothelialВ cells,В andВ ganglionВ cells
Normal
Functions: • Promotes proliferation, migration, and capillary tube formation…but not maturation
• Increases vascular permeability
Stimuli:
• Normal physiology (including trophic maintenance of choriocapillaris)
• Hypoxia
• Inflammation?
• Structurally sound
• Targeted direction
• Visually necessary
• Bruch’s deposits
• CNV in choroiditis
• But not all choroiditides
causeВ CNV
vs.
Hypoxia
• Diffuse thickening of Bruch’s
• But not all CNVs due to hypoxia
PrevailingВ theories
Disruption of Bruch’s Membrane
AlteredВ RPEВ andВ ECMВ metabolism
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
• Incompetent
• Invasive, lacking taxis
• Visually destructive
RecentВ paradigmВ shift
Probably not…
Inflammation
Pathologic
Very delicate homeostasis…
SoВ whatВ tipsВ theВ balance?
AreВ allВ CNVMsВ createdВ equal?
ChoroidalВ neovascularizationВ isВ poorlyВ characterizedВ andВ poorlyВ understood.
V
E
G
F
Surgical
CNVMВ excision
MacularВ translocation
Anti‐inflammatory
Triamcinolone
Ablative
LaserВ photocoagulation
PhotodynamicВ therapy
Molecular (Anti‐VEGF)
Macugen (pegaptanib)
LucentisВ (ranibizumab)
AvastinВ (bevacizumab)
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LatestВ therapeuticВ agents
VEGFВ TrapВ (aflibercept)
• FDA approved for exudative AMD
• High affinity to most members of VEGF family, including PlGF
• Less frequent dosing schedule than current anti‐
VEGFВ meds
• Efficacy comparison to Lucentis still ongoing…
PatientВ Update
RNAВ Interference
• Bevasirinib
– Inhibition of VEGF through RNA interference
– Upstream mechanism causes delayed onset of activity; not superior to current meds
• AGN211745 (Sirna‐027)
– Inhibition of VEGFR‐1 through RNA interference
– Studies ongoing BCVA:   20/150 to 20/80 s/p Avastin x 3
ClinicalВ Pearls
• Know the clinical signs that signal presence of CNVM:
– PED, RPE irregularity, subretinal fluid, CME, lipid exudation, and subretinal hemorrhage
• VEGF is only one of likely many inciting factors that can initiate CNVM, and not all CNVMs are created the same.
• Long‐term blockade of VEGF may accelerate choriocapillaris atrophy. Other therapeutic mechanisms need to be discovered.
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
References
•
•
•
•
•
•
•
•
Do DV. Detection of new‐onset choroidal neovascularization. Curr Opin Ophthalmol. 2013 May;24(3):244‐7. PubMed PMID: 23518615. Do DV, Gower EW, Cassard SD, Boyer D, Bressler NM, Bressler SB, Heier JS, Jefferys JL, Singerman LJ, Solomon SD. Detection of new‐onset choroidal neovascularization using optical coherence tomography: the AMD DOC Study. Ophthalmology. 2012 Apr;119(4):771‐8. PubMed PMID: 22297028. Kinnunen K, Ylä‐Herttuala S. Vascular endothelial growth factors in retinal and choroidal neovascular diseases. Ann Med. 2012 Feb;44(1):1‐17. PubMed PMID: 21284527. Qazi Y, Maddula S, Ambati BK. Mediators of ocular angiogenesis. J Genet. 2009 Dec;88(4):495‐515. PubMed PMID: 20090210; PubMed Central PMCID: PMC3306772. Campochiaro PA. Retinal and choroidal neovascularization. J Cell Physiol. 2000 Sep;184(3):301‐10. PubMed PMID: 10911360. Spaide RF. Choroidal neovascularization in younger patients. Curr Opin Ophthalmol. 1999 Jun;10(3):177‐81. PubMed PMID: 10537776. D'Amore PA. Mechanisms of retinal and choroidal neovascularization. Invest Ophthalmol Vis Sci. 1994 Nov;35(12):3974‐9. PubMed PMID: 7525506. Gass JM. Stereoscopic Atlas of Macular Diseases. 3 ed. Klein EA editor. St. Louis, Missouri: Mosby; 1987. 63
6/11/2013
MyopiaВ Prevalence1
Pediatric
Myopia
Modulation
Alex J Smith, OD, FAAO
Diplomate, American Board of Optometry
UC Berkeley Dr. Michael G Harris Contact Lens Resident
IncreasingВ prevalenceВ ofВ myopia
RisksВ ofВ highВ myopia
• “Myopia has reached epidemic proportions.”3
– Ophth Physiol Optics. September 2005
• Public Health Ramifications3,4
• Taiwanese schoolchildren2: –
–
–
–
Year 2000: 84% 16‐18 yr olds myopic
Year 1983: 74% 16‐18 yr olds myopic
YearВ 2000:В 21% HighВ (>6.00D)В myopiaВ atВ 18В yrs old
YearВ 1983:В 10.9% HighВ (>6.00D)В myopiaВ atВ 18В yrs old
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
–
–
–
–
–
–
–
–
–
–
RetinalВ detachment
POAG
Maculopathy
DiscВ anomalies
LacquerВ cracks/CNVM
MacularВ hole
Staphyloma
Cataracts
ReducedВ visualВ quality
LifetimeВ $В forВ treatment
64
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PeripipheralВ HyperopicВ DefocusВ vs.В LagВ ofВ accommodation
• In both cases, light is focused behind the retinal plane
CLAMPВ STUDY5
• RGPs for Myopia Control
– Not effective
• Peripheral hyperopic defocus
– When optical correction is in place, central rays focus centrally
– Peripheral rays focus behind the retina
• No plus in it
• Lag of accommodation
– Transient central hyperopic defocus
– Higher levels of education associated with myopia
COMETВ StudyВ 20036
• +2.00 add PAL
– Small area of plus power
• Overall 0.20 D difference (14%) over 3 years
2008В OEPВ NorthwestВ Congress
• Aller & Wildsoet twin study7
– Acuvue bifocal (putting plus on it)
– Statistically significant but “not clinically significant”
– Occurred in first year
• Higher efficacy if high lag of accommodation + lower baseline myopia
– 0.48 D difference
• Highest efficacy if high lag of accommodation + eso
– 0.64 D difference
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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ImageВ shell8
Image shell ‐ Orthokeratology
9
LORICВ STUDYВ 200510
2008В OEPВ NorthwestВ Congress
• Atropine intervention
– Chua 200611
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COMETВ 2В StudyВ 201112
• 0.28 D 3‐year difference
Cambridge Anti‐Myopia Study 201313,14
• “Peripheral Refractive Changes Associated with Myopia Progression” IOVS Feb 2013
• No difference in myopic progression between any arm
• No plus power (myopic defocus) applied to retina
Hiraoka etВ alВ 201215
ReducedВ concentrationsВ ofВ Atropine
• Chia et al 201216
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WhatВ canВ anyВ ODВ doВ forВ PatientsВ Tomorrow?
• Atropine 0.1%
References
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– Best balance of efficacy vs. side effects
– 0.01% minimal side effects for similar efficacy to O‐K, MF soft
• Orthokeratology
– Topographer needed
– Overnight lens wear risks
• Multifocal soft contact lenses
– Distance center has most evidence
• Executive bifocal glasses with 3^BI
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• When in doubt...
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1. Santodomingo, J. “Controlling Myopia Progression in Children” Menicon Horizons. 2011 May; 6.
2. Lin, LLK et al. “Prevalence of Myopia in Taiwanese Schoolchildren: 1983‐2000.” Annals Academy of Medicine. 2004 Jan;33(1):27‐33.
3. Saw, S‐M, et al. “Myopia and associated pathological complications.” Ophthal Phys Optics. 2005 Sept;22(5):381‐391
4. Kanski, Jack J. Clinical Ophthalmology. 5th Ed. Butterworth‐Heinemann. 2003
5. Walline, Jeffrey J et al. “A Randomized Trial of the Effects of Rigid Contact Lenses on Myopia Progression.” Arch Ophthalmol. 2004;122:1760‐1766.
6. Gwiazda, Jane. “Treatment Options for Myopia.” Optom Vis Sci. 2009 June;86(6):624‐628
7. Aller, TA. “Myopia Progression in a Twin Pair with Bifocal Soft Contact Lenses – Second Year Results After Single Crossover.” <http://www.aaopt.org/Submission/Search/SubmissionViewer.asp?SID=4203&BR=SP>
8. Smith, E. “Prentice Award Lecture 2010: A Case for Peripheral Optical Treatment Strategies for Myopia.” Optom Vis Sci. 2011 Sept;88(9):1029‐1044.
9. Herzberg, C. “An Update on Orthokeratology.” Contact Lens Spectrum; 2010 Mar. http://www.clspectrum.com/articleviewer.aspx?articleid=103967
10. Cho, P et al. “The longitudinal orthokeratology research in children (LORIC) in Hong Kong: a pilot study on refractive changes and myopic control.” Curr Eye Res. 2005 Jan;30(1):71‐80.
11. Chua, WH et al, “Atropine for the treatment of childhood myopia.” Ophthalmology. 2006 Dec;113(12):2285‐91.
12. PEDIG. “Progressive‐Addition Lenses vs. Single‐Vision Lenses for Slowing Progression of Myopia in Children with High Accommodative Lag and Near Esophoria.” IOVS. 2011 April;52(5):2749‐2757
13. Radhakrishnan, H. et al. “Peripheral Refractive Changes Associated with Myopia Progression.” IOVS. 2013 Feb;54(2):1573‐81
14. Allen, PM. Et al. “Aberration Control and Vision Training as an Effective Means of Improving Accommodation in Individuals with Myopia.” IOVS. 2009 Nov;50(11):5120‐5129.
15. Hiraoka, T. et al, “Long‐Term Effect of Overnight Orthokeratology on Axial Length Elongation in Childhood Myopia: A 5‐
Year Follow‐Up Study.” IOVS. 2012 June;53(7):3913‐3919
16. Chia, A. et al. “Atropine for the treatment of Childhood Myopia: Safety and Efficacy of 0.5%, 0.1% and 0.01% Doses (Atropine for the Treatment of Myopia 2).” Ophthalmology. 2012 Feb;119(2):347‐354.
PrimaryВ OcularВ HSV
• Subclinical in 94% Re‐thinking HSV Keratitis
• Bimoidal distribution
– Ages 1‐5; Ages 13‐25
• Lid vesicles or erosive blepharitis (34‐
44%)
AndreaВ DeВ Souza,В O.D.
PrimaryВ CareВ andВ ContactВ LensВ Resident
UCВ BerkeleyВ SchoolВ ofВ Optometry
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
• Epithelial keratitis (15‐63%)
• Follicular or pseudomembraneous
conjunctivitis (54‐84%)
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UnilateralВ orВ Bilateral?
HSVВ EpithelialВ Keratitis
• 50‐80% ocular HSV
• Souza: 98% unilateral
• Three types:
• Wilhelmus: 97% unilateral
– Bilateral HSV is undefined
– Bilateral herpetic keratitis: presence of dendritic or geographic epithelial ulceration
– Stellate
– Dendritic (9‐15%)
– Geographic
• Brandt: 88.2% unilateral
• Rezende:87.8% unilateral
• Darougar: 81% unilateral
– Bilateral herpetic keratitis: any form of HSV keratitis
Management:В GoldВ Standard
• Orals:
– 400mg Acyclovir 5x/d
– 500mg Valacyclovir TID
– 250mg Famciclovir TID
• Topicals:
– 1% Trifluridine 9x/d
– 0.15% Gancyclovir 5x/d
1%В TrifluridineВ (Viroptic)
• Thimerosol preservative
–
–
–
–
CornealВ toxicityВ (punctateВ keratopathy)
BurningВ orВ stingingВ (4.6%)
CornealВ edema
Conj.В edema,В hyperemia
• Compliance?
• Consumer availability?
• Cost: ~$100 (7.5mL)
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0.15%В Gancyclovir GelВ (Zirgan)
п‚—
BAKВ preservative
в—¦ IrritationВ (20%)
в—¦ SPKВ (5%)
в—¦ HyperemiaВ (5%)
п‚—
п‚—
Compliance?
Cost:В ~$170В (1В tube,В 5gm)
OralВ and/orВ TopicalВ Acyclovir
TopicalВ Steroids?
• Stromal keratitis and endotheliitis? Yes.
• Epithelial keratitis? NO!
• Complications:
– Enlargement of stellate
lesionsВ orВ dendrites
– Progression to necrotizing stromal keratitis
– Iritis or hypopyon
– Secondary GLC
Photo
ODВ vs OMDВ Management
• HEDS 2: Trifluridine and 400mg acyclovir
– no benefit in preventing stromal keratitis or iritis
• Collum L.: 3% acyclovir ophthalmic ointment vs. 400mg oral acyclovir – no statistically significant difference in the median time to healing
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
GroupВ 1:В OD
GroupВ 2:В OMDВ withoutВ corneaВ fellowship
GroupВ 3:В OMDВ withВ corneaВ fellowship
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Pros:
‐
‐
TopicalВ Antivirals
‐
EasierВ toВ administer
LowerВ systemicВ penetration
Costly
‐ Trifluridine: $100
‐ Gancyclovir: $170
Cons:
‐
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FrequentВ dosingВ (trifluridine)
GreaterВ ocularВ sideВ effects
RefrigerationВ (trifluridine)
Oral Antivirals
Pros:
Cons:
‐
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‐
‐
‐
‐
‐
LessВ frequentВ dosing
FewerВ sideВ effects
‐ Metabolized by kidneys
NoВ refrigeration
Cost
‐ Acyclovir: $20
‐ Valacyclovir: $200
ReducesВ systemicВ viralВ load
PenetratesВ multipleВ ocularВ tissues
DifficultВ toВ swallow
AlternativeВ ManagementВ OralВ Antivirals
Pros:
Cons:
‐ Less frequent dosing
‐ Fewer side effects
‐ Difficult to swallow
‐ Metabolized by kidneys
‐ No refrigeration
‐ Cost
‐ Acyclovir: $20
‐ Valacyclovir: $200
‐ Reduces systemic viral load
‐ Penetrates multiple ocular tissues
FluoroquinolonesВ forВ HSV
• Primary or recurrent HSV:
– 800mg Acyclovir 5x/d (10 days)
• Faster healing time
• No increased side effects
• DNA‐topoisomerase
cleavage complexes • Structural similarities between topoisomerases of DNA viruses and bacteria
• HSV 1 and 2: – dsDNA virus – uses topoisomerase I & II
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
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п‚—
AfricanВ SwineВ FeverВ Virus:В п‚—
п‚—
Method:
п‚—
п‚—
NoВ viralВ genomeВ fragmentationВ observed
п‚—
ProposedВ MOA:В ASFVВ topoisomerase IIВ inhibitor
DNAВ encodesВ forВ topoisomerase II
injectВ animalВ cellsВ withВ 30В fluoroquinolonesВ atВ varyingВ timesВ afterВ infection
interferenceВ withВ ATPase activity
torsional/replicative stress
п‚— reductionВ inВ viralВ DNAВ replicationВ andВ proteinВ synthesis
п‚—
п‚—
п‚—
NoВ viralВ genomeВ fragmentationВ observed
п‚—
ProposedВ MOA:В ASFVВ topoisomerase IIВ inhibitor
interferenceВ withВ ATPase activity
torsional/replicative stress
п‚— reductionВ inВ viralВ DNAВ replicationВ andВ proteinВ synthesis
п‚—
п‚—
ReviewingВ Differentials
CanВ fluoroquinolonesВ haveВ aВ similarВ effectВ onВ HSV?
HSV EpithelialВ Keratitis
Microbial Keratitis
Unilateral orВ bilateral
Unilateral
Stellate lesions
• multiple, elevated
Infiltrate/ulcer
• single, excavated
Greater corneal orВ lidВ edema
CanВ fluoroquinolonesВ temporarilyВ reduceВ hostВ cellВ replication?
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
Tx:В antivirals
Tx:В antibiotics
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ReviewingВ Differentials
HSV EpithelialВ Keratitis
Infiltrative Keratitis
Unilateral orВ bilateral
Unilateral orВ bilateral
Stellate lesions
• multiple, elevated, irregular shape
PinpointВ lesions
• multiple, flat, round
References
•
•
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Greater corneal orВ lidВ edema
Tx:В antivirals
Tx:В steroids
•
•
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•
•
•
•
•
•
UCВ BERKELEYВ RESIDENTВ FORUMВ JUNEВ 2013
National Eye Institute. “Herpetic Eye Disease Study (HEDS 1/2)”. U.S. National Institutes of Health.  Sept 1999.  Bernstein, D. et al. “Epidemiology, Clinical Presentation, and Antibody Response to Primary Infection With Herpes Simplex Virus Type 1 and Type 2 in Young Women”.  Clinical Infectious Diseases. February 1, 2013; 56(3):344–51
Souza, P. et al. “Bilateral Herpetic Keratoconjunctivitis”. American Academy of Ophthalmology. March 2003. Vol 110, Num. 3, Pgs. 493‐496.
Remeijer, L. et al. “Human herpes simplex virus keratitis: the pathogenesis revisited”. Ocular Immunology and Inflammation – 2004, Vol. 12, No. 4, pp. 255–285
Saini, J. and Argawala, R. “Clinical Pattern of Recurrent Herpes Simplex Keratitis”. Indian Journal of Ophthalmology. 1999. Vol: 47, Issue:1. Pg 11‐14. Wilhelmus, K. “Bilateral herpetic keratitis”. British Journal of Ophthalmology, 1981, 65, Pgs. 385‐387. Liesegang, L. “Herpes Simplex Virus Epidemiology and Ocular Importance”. Cornea (2001).  20(1): 1–13, 2001.
Sacks, S. et al. “Clinical Management of Herpes Virus”. IOS Press. Netherlands. 1995. Pg. 23
Darougar, S. et al.   “Epidemiological and clinical features of primary herpes simplex virus ocular infection”. British Journal of Ophthalmology, 1985, 69, Pgs. 2‐6.
Farooq, A. and Shukla, D. “Herpes Simplex Epithelial and Stromal Keratitis: An Epidemiologic Update”. Survey of Ophthalmology. October 2012. Vol. 57, Number 5, Pgs. 448‐461.
Potter, W. “An Overview of Ocular Herpetic Disease”. Review of Optometry. May 2010.
Thygeson, P. et al. “The Unfavorable Response of Topical Steroid Therapy on Herpetic Keratitis”. Transactions of the American Ophthalmological Society. 1960; 58: 246–256.
Kimura, S. et al. “Herpes Simplex Keratitis: An Experimental Study”. Investigative Ophthalmology. April 1962. Pgs 273‐278.
Lee. S. and Pavan‐Langston, D. “Role of Acyclovir in the Treatment of Herpes Simplex Virus Keratitis”. International Ophthalmology Clinics. 1994. Volume 3, Issue 3. Pgs 9‐18.
Collum, L. et al. “Oral Acyclovir (Zovirax) in Herpes Simplex Dendritic Corneal Ulceration”. British Journal of Ophthalmology. 1986; 70. Pgs 435‐438. Mottola, C. et al. “In Vitro Antiviral Activity of Fluoroquinolones Against African Swine Fever Virus”. Veterinary Microbiology. 2013. Pgs 1‐9.
Bapat, A. et al. “Studies on DNA Topoisomerases I and II in Herpes Simplex Virus Type 2‐ infected Cells”. Journal of General Virology.1987. Vol. 68. Pgs 2231‐2237.
Ebert, S. et al. “Topoisomerase II Cleavage of Herpes Simplex Virus Type1 DNA In Vivo Is Replication Dependent”. Journal of Virology. Sept. 1990. Vol. 64, No.9.  Pgs 4059‐4066
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