Author: Dr. Geary Rummler, OD - Northport VAMC Optometric Resident Co-Author: Dr. Mark Hakim, OD - Northport VAMC Optometric Resident Title: A Complicating Case of Glaucoma Suspicion Confounded by Advanced Stargardt’s Disease: Testing and Alternatives for Appropriate Management. Abstract: The profile and testing for Glaucoma is well established, specifically for patients with average vision. This case-report investigates instruments and alternatives that should be emphasized for patients with advanced Stargardt’s Disease and Glaucoma Suspicion. I. Case History • Patient Demographics: 56 year old African American Male • Chief Complaint: Reduced vision, light sensitivity, and difficulty finding things he dropped or misplaced. • Ocular/Medical History: Advanced Stargardt’s, Glaucoma Suspicion, Borderline Diabetes, Hyperlipidemia, Hypertension, Depressive disorder, Back/lumbosacral pain, and Obesity • Medications: Artificial tears, Aspirin, Atenolol, Hydrochlorothiazide, Simvastatin • Other Salient Information: Legally blind under the U.S. Definition and accompanied by guide-dog II. Pertinent Findings • Clinical: Visual Acuity OD: 5ft/63 OS: 5ft/80 with illuminated Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Pupils, EOMs, and slit lamp examination within normal limits. Intraocular Pressure (IOP) 13/13 mm Hg taken by applanation tonometry AM pressure reading. • Physical: Dilated fundus exam (DFE) - optic nerve head (ONH) appearance 0.7 cup to disk ratio with even superior and inferior rim tissue, well perfused, thinnest rim temporally OU. Macula central patch of geographic atrophy OU. Yellow-white flecks pisciform shape scattered throughout posterior pole. • Laboratory Studies: Octopus Visual Field, Goldmann Kinetic Visual Field • Radiology Studies: Fundus Photography, Heidelberg OCT Macula and OCT ONH retinal nerve fiber layer • Others: IOP historical maximum 19/18 mm Hg, Pachymetry 543/533, family history of glaucoma III. Differential Diagnosis • Primary/Leading: Glaucoma suspect secondary to optic nerve appearance and positive family history • Others: Primary Open Angle Glaucoma (POAG), Mixed Mechanism Glaucoma (MMG) IV. Diagnosis and Discussion Elaborate on the condition: • Stargardt’s Disease is a progressive hereditary macular dystrophy. Symptoms initially present within the first two decades of life and progress throughout adulthood. Central acuity declines and ultimately maintains vision worse than 20/200. Physical presentation includes generally symmetric geographic atrophy and retinal thinning of the maculae. Furthermore, characteristic yellow-white flecks fish-tailed or pisciform in morphology are scattered throughout the posterior poles. The etiology involves a number of mutations within the ABCA4 gene located on chromosome one. ABCA4 encodes for a protein transporter, which removes all-trans-retinal from the disk outer segment to the photoreceptor cytoplasm. The mutated gene creates faulty transportation and build-up of cytotoxic all-trans-retinal, resulting in cell death of retinal-pigmented epithelium and photoreceptors. • Glaucoma is an overarching condition, which causes visual damage secondary to retinal ganglion cell death and optic nerve fiber thinning. The believed pathogenesis involves increased intraocular pressure secondary to impeded aqueous outflow or increased production. This build-up puts pressure on the lamina cribrosa of the optic nerve where retinal ganglion cells exit. Such impingement can damage and compromise axonal transport and subsequent retrograde transport of essential trophic factors to retinal ganglion cells. Glaucoma’s visual symptoms are variable in severity, however its general affects begin with peripheral field defects and encroach centrally in advanced cases. Expound on unique features: • Consider the advanced central vision loss secondary to Stargardt’s coupled with peripheral visual defects caused by Glaucoma. Although no treatment for preventing central vision loss in Stargardt’s exists; management to delay peripheral vision loss for Glaucoma does. Therefore it is imperative to cautiously monitor the patient’s visual degeneration to prevent further loss of vision. • The management for Glaucoma classically entails a profile of risk factors and testing. Visual field testing relies heavily on a patient’s subjective understanding and ability to fixate on a central target. Considering the patient’s legal blindness and central scotoma, fields both kinetic and static have proven unreliable and inconclusive. Alternatively OCT provides objective and structural progression analysis. However, due to the advanced atrophic areas and retinal thinning, OCT ganglion cell and retinal nerve fiber layer measurements are artificially low. Other forms of objective testing must be emphasized and considered as the best management for treatment. V. Treatment/Management • Assessment of the patient’s POAG suspicion was maintained as low risk, and likely optic nerve head appearance secondary to physiological cupping. Risk factors such as race and positive family history were considered, along with the inconclusive visual fields and skewed OCT analysis confounded by Stargardt’s. A profile of normotensive IOP history, slightly below average corneal pachymetry, and stable ONH appearance apparent on DFE and fundus photography support the continued monitoring of the patient without medical or surgical intervention. • Due to the patients confounding visual diagnoses and sensitivity in regards to remaining vision, consultation with Ophthalmologic Glaucoma Specialists was recommended. If deemed necessary to follow-up and maintain care in Ophthalmology, objective testing was advocated as the best means for monitoring progression. • A cross-sectional survey sought to analyze efficacy of using optic nerve head stereo-photography as an indicator for differentiating control healthy eyes versus glaucomatous or suspect eyes. Control, Suspect, and diagnosed Glaucoma patients were categorized by static visual field (VF) and spectral- domain OCT (sdOCT) results. Glaucoma specialists were masked to the results of VF/sdOCT and asked to grade optic nerve photos based on a number of glaucomatous optic neuropathic (GON) features. Classification of such features via stereo-photography was deemed able to differentiate healthy eyes from those defined as suspected/ glaucomatous within the study1. • A compilation of case reviews analyzes the objective findings of visual electrophysiology and which testing provides sensitive and specific information in regards to glaucoma. The article provides a comprehensive review of multifocal ERG (mfERG), photopic negative response (PhNR), pattern ERG (PERG), multifocal pattern ERG (mfPERG), and multifocal VEP (mfVEP). The article suggests single- patient assessment can be clinically indicated using PhNR, PERG, or mfVEP. Although sensitivity and specificity for these tests are questionable, the results are comparable to visual field indices of early glaucoma and have potential in unique cases2 • Bibliography: 1. Alhadeff PA, De Moraes CG, Chen M, et al. The Association Between Clinical Features Seen on Fundus Photographs and Glaucomatous Damage Detected on Visual Fields and Optical Coherence Tomography Scans. Journal of Glaucoma 26.5 (2017): 498-504. 2. Bach M, Poloschek CM. "Electrophysiology and Glaucoma: Current Status and Future Challenges." Cell and Tissue Research 353.2 (2013): 287-96. VI. Conclusion • Clinical pearls, take away points if indicated: The central scotoma secondary to Advanced Stargardt’s combined with the potential of peripheral vision loss with POAG suspicion creates a dangerous duality. A need exists for sensitive and reliable monitoring. Due to the difficulty with subjective visual field testing and confounded OCT findings, management must be modified. Referencing scientific articles, optic nerve photography and visual electrophysiology provide possibilities for alternative yet appropriate management for this patient.