RETINAL DEPOSITS OF TRIAMCINOLONE-MOXIFLOXACIN AFTER DROPLESS CATARACT SURGERY.

PURPOSE: To report a case of epiretinal crystalline deposits observed on fundus examination and optical coherence tomography 2 years after transzonular intravitreal injection of triamcinolone-moxifloxacin (TriMoxi) during "dropless" cataract surgery. METHODS: Observational case report with literature review of toxic effects of intravitreal triamcinolone and differential diagnosis of retinal crystalline deposits. RESULTS: A 37-year-old asymptomatic pseudophakic man presented with refractile crystalline retinal deposits that had prompted an extensive systemic embolic workup. The systemic evaluation for emboli was negative. OCT imaging revealed that the crystalline deposits were confined to the anterior surface of the internal limiting membrane. Further historical inquiry determined that transzonular intravitreal triamcinolone-moxifloxacin injection had been performed at the time of cataract surgery 2 years earlier. CONCLUSION: Transzonular triamcinolone acetonide delivered during cataract surgery can deposit on the retinal surface for long periods. These epiretinal crystalline deposits are benign and generally do not interfere with visual acuity. Nevertheless, clinicians should be aware of this differential diagnosis because clinical misdiagnosis can lead to unwarranted evaluation and treatment.

Positive feedback loop between vision-related anxiety and self-reported visual difficulty.

BACKGROUND: Patients with Inherited Retinal Diseases typically experience progressive, irreversible vision loss resulting in low vision and blindness. As a result, these patients are at high risk for vision-related disability and psychological distress, including depression and anxiety. Historically, the relationship between self-reported visual difficulty (encompassing metrics of vision-related disability and quality of life, among others) and vision-related anxiety has been regarded as an association and not a causal relationship. As a result, there are limited interventions available that address vision-related anxiety and the psychological and behavioral components of self-reported visual difficulty. MATERIALS AND METHODS: We applied the Bradford Hill criteria to evaluate the case for a bidirectional causal relationship between vision-related anxiety and self-reported visual difficulty. RESULTS: There is sufficient evidence to satisfy all nine of the Bradford Hill criteria of causality (strength of association, consistency, biological gradient, temporality, experimental evidence, analogy, specificity, plausibility, and coherence) for the relationship between vision-related anxiety and self-reported visual difficulty. CONCLUSIONS: The evidence suggests that there is a direct positive feedback loop-a bidirectional causal relationship-between vision-related anxiety and self-reported visual difficulty. More longitudinal research on the relationship between objectively-measured vision impairment, self-reported visual difficulty, and vision-related psychological distress is needed. Additionally, more investigation of potential interventions for vision-related anxiety and visual difficulty is needed.

The validation of inherited retinal disease-specific patient-reported outcome measures in adolescent patients.

PURPOSE: To determine the validity of the validate the adult patient-reported outcome measure tools, the Michigan Retinal Degeneration Questionnaire (MRDQ) and Michigan Vision-Related Anxiety Questionnaire (MVAQ), in adolescent patients with inherited retinal diseases (IRDs). METHODS: Ninety-one adolescent patients diagnosed with IRDs were recruited at the Hospital for Sick Children (University of Toronto) and the Kellogg Eye Center (University of Michigan). The patients were administered the MRDQ, MVAQ, and Patient Health Questionnaire-4 (PHQ-4). Test-retest variability was assessed in eighteen patients within 14 days of the initial administration. Adolescent responses were analyzed for validity and reliability. As a further validation step, comparisons were made to adult data from the original MRDQ and MVAQ studies to ensure consistency in response ranges. RESULTS: The existing MRDQ and MVAQ content and format could accurately detect the impact of IRD on activities of daily living in adolescents with IRDs. No floor/ceiling effects were identified, test-retest reliability was established (r = 0.73-0.86), and no items were excluded after differential item functioning analysis. Domain and trait associations with visual acuity and IRD phenotypes were similar between adolescents and adults. CONCLUSIONS: The MRDQ and MVAQ are psychometrically validated questionnaires for which we have shown validity for use in adolescent patients with IRDs.

Self-reported visual function and psychosocial impact of visual loss in EYS-associated retinal degeneration in a Portuguese population.

PURPOSE: To evaluate self-reported visual function and the psychosocial impact of visual loss EYS-associated retinal degeneration (EYS-RD) using two patient-reported outcome (PRO) measures: Michigan Retinal Degeneration Questionnaire (MRDQ) and Michigan Vision-related Anxiety Questionnaire (MVAQ). METHODS: Cross-sectional, single-center study conducted at a tertiary care hospital in Portugal. Patients with biallelic EYS variants were invited to participate. Clinical data including demographics, ETDRS best-corrected visual acuity (BCVA) in the better-seeing eye and genetic testing results were collected. Interviews were carried out during clinic visits or by phone between November 2021 and February 2022. A blind grader used horizontal and vertical spectral domain optical coherence tomography (SD-OCT) scans to manually measure ellipsoid zone (EZ) width in the nasal, temporal, superior and inferior macular quadrants to calculate the EZ area. RESULTS: Forty-nine patients (53.1% males; mean age 53 ± 14 years) were included. A positive correlation (p < .05) was found between age and most MRDQ domain scores (central vision, color vision, contrast sensitivity, scotopic function, photopic peripheral vision and mesopic peripheral vision). A negative correlation was found between both BCVA and EZ area across all MRDQ domains. In MVAQ, SD-OCT EZ area negatively correlated with both rod function and cone function-related anxiety. Neither age, BCVA or gender correlated with MVAQ domains. CONCLUSIONS: This study provides strong evidence supporting a correlation between PRO measures and both functional and structural clinician-reported outcomes. The use of MRDQ and MVAQ adds a new dimension to our understanding of EYS-RD and establishes both PRO measures as important disease outcome measures.

Construct Validity of Inherited Retinal Disease-Specific Patient-Reported Outcome Measures.

PURPOSE: To evaluate aspects of construct validity of the Michigan Retinal Degeneration Questionnaire (MRDQ) and the Michigan Vision-related Anxiety Questionnaire (MVAQ). METHODS: Subjects with a clinical diagnosis of an inherited retinal disease (IRD) were recruited prospectively and 3 tests were used to assess construct validity: the ability to distinguish different IRD phenotypes; test a priori hypothesis of an association between vision-related anxiety and vision-related disabilities; and correlate MRDQ and MVAQ with the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) and the Impact of Vision Impairment (IVI). One-way analysis of variance (ANOVA) was used to compare different phenotypes for mean domain scores for MRDQ/MVAQ. Pearson correlations were performed between; Cone-Function Anxiety and Central Vision controlling for better eye visual acuity, Rod-Function Anxiety and Scotopic Function controlling for visual field area (III4e and IV4e), and scores of MRDQ/MVAQ, NEI VFQ-25, and IVI. RESULTS: The study sample consisted of 146 patients evenly divided between males and females, and mean age was 50 years. The 1-way ANOVA test was significant for distinguishing IRD phenotypes in 6 domains of MRDQ/MVAQ. Cone-Function Anxiety correlated with Central Vision controlling for visual acuity, Rod-Function Anxiety correlated with Scotopic Function controlling for visual field area, and all domains in MRDQ/MVAQ had significant correlations with NEI VFQ-25 and IVI composite scores. CONCLUSION: MRDQ and MVAQ domenstrate aspects of construct-validity set forth by the US Food and Drug Administration. The study futher supports the use of both patient-reported outcome measures in IRD clinical trials and natural history studies.NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Effects of duration and number of symptoms on vision-related anxiety in patients with Inherited Retinal Diseases.

BACKGROUND: Patients with Inherited Retinal Diseases (IRDs) are at increased risk for vision-related anxiety due to progressive and irreversible vision loss, yet little is known about risk factors for anxiety in these patients. MATERIALS AND METHODS: This was a single-center, retrospective cross-sectional study at a large academic center. 128 adults with an IRD and without other significant eye conditions were recruited between December 2016 and March 2020. Participants were asked about the duration and number of symptoms they had in the following vision domains: reading, contrast vision, color vision, glare/light sensitivity, night vision, and peripheral vision. The outcomes of interest were the two domains of the Michigan Vision-Related Anxiety Questionnaire (MVAQ), rod- and cone-function related anxiety. We conducted an adjusted analysis to isolate the independent effect of duration and number of symptoms on vision-related anxiety. RESULTS: Of 126 participants had complete data, 62 (49%) were female and 64 (51%) were male, with an average age of 49 years (range: 18-87). Patients with duration of symptoms for greater than 25 years had an adjusted anxiety theta that was one-half standard deviations lower than patients with symptoms for less time. Patients with higher number of symptoms had higher anxiety theta after adjusting for confounding variables (p < 0.0001). CONCLUSIONS: The number of symptoms but not the duration of symptoms, is an independent risk factor for vision-related anxiety. Patients with more symptoms are at higher risk for vision-related anxiety. Having symptoms for longer than 25 years may reduce this anxiety.

Question: How does the duration and number of symptoms that patients with Inherited Retinal Diseases have affect their vision-related anxiety?Findings: In this cross-sectional study of 126 patients with Inherited Retinal Diseases, the number of symptoms, but not the duration of symptoms, was associated with higher vision-related anxiety. Patients with symptoms for longer than 25 years had less vision-related anxiety.Meaning: Patients with more vision-related symptoms may experience more vision-related anxiety.

Challenges of Cost-Effectiveness Analyses of Novel Therapeutics for Inherited Retinal Diseases.

PURPOSE: To investigate the challenges and potential improvement strategies of cost-effectiveness analyses performed for therapeutics targeting inherited retinal diseases (IRDs). DESIGN: Perspective. METHODS: A literature review was conducted with discussion of current limitations and improvement recommendations. RESULTS: Cost-effectiveness analysis (CEA) performed for IRD therapeutics has multiple limitations. First, the available methods used to measure health-related quality of life and health utilities can be inaccurate when used in IRDs. Second, the financial burden to patients and society from vision impairment associated with IRDs has been inadequately studied and includes a variety of expenditures ranging from direct costs of IRD specialty health care to indirect expenses associated with daily living activities. Third, our collective understanding is limited in the areas of IRD natural history and health benefits gained from new IRD treatments (eg, gene therapies). In addition, the therapeutic effect from a patient perspective and its duration of action are not fully understood. Due to the scarcity of data, CEA for newly approved therapies has relied on assumptions and creations of predictive models for both costs and health benefits for these new therapeutics in order to calculate the incremental cost-effectiveness ratio. CONCLUSIONS: CEA studies performed for IRD therapeutics have been limited by the established health utilities in ophthalmology and the lack of disease-specific information. The assumptions and extrapolations in these studies create substantial uncertainty in incremental cost-effectiveness ratio results. An improved framework is required for CEA of IRD therapeutics in order to determine the cost-effectiveness of each therapy brought from clinical trials to clinical practice.

Prevalence of Focal Inner, Middle, and Combined Retinal Thinning in Diabetic Patients and Its Relationship With Systemic and Ocular Parameters.

Purpose: To determine the prevalence of focal inner, middle, and combined inner/middle retinal thinning (FIRT, FMRT, and FCRT, respectively) in different stages of diabetic retinopathy (DR) without diabetic macular edema and to assess the relationship between such findings with ocular and systemic parameters. Methods: This was a cross-sectional, comparative study comprising healthy participants and diabetic patients with different stages of DR. Forty-nine horizontal macular B-scans from the selected eye were obtained using spectral-domain optical coherence tomography (SD-OCT) and analyzed for the presence of FIRT, FMRT, or FCRT and any relationship with systemic and ocular parameters. Focal retinal thinning (FRT) was subjectively defined as any evidence of inner and/or middle retinal thinning. Results: A total of 190 participants (52 healthy participants and 138 diabetic patients) were included. A higher prevalence of FRT was observed in eyes with advanced DR versus healthy eyes and versus diabetic eyes with no DR or mild DR. FIRT and FCRT were significantly greater in eyes with proliferative DR treated with pan-retinal photocoagulation, and FMRT was significantly more common in eyes with severe nonproliferative DR. FRT was significantly more common in patients with coronary artery disease and was positively correlated with diabetes duration, serum creatinine, and glycosylated hemoglobin and negatively correlated with age, estimated glomerular filtration rate, and visual acuity. Conclusions: FRT occurs in all stages of DR and is increasingly prevalent with increasing severity of DR. Translational Relevance: OCT identification of FRT may provide a surrogate biomarker of retinal and systemic disease in diabetic patients.

The Michigan Retinal Degeneration Questionnaire: A Patient-Reported Outcome Instrument for Inherited Retinal Degenerations.

PURPOSE: To create a psychometrically validated patient-reported outcome measure for inherited retinal degenerations. DESIGN: Qualitative and quantitative patient-reported outcome (PROs) questionnaire development using item response theory validation. METHODS: One hundred twenty-eight patients with a diagnosis of an inherited retinal degeneration at the Kellogg Eye Center (University of Michigan) were recruited and administered a 166-item questionnaire comprising 7 expert-defined domains. The questionnaire was re-administered 4-16 days later to a subset of 25 participants to assess test-retest variability. Graded response models were fit by Cai's Metropolis-Hastings Robbins-Monro algorithm using the R (version 3.6.3) package mirt. Model data were fit to assess questionnaire dimensionality, to estimate item information, and to score participants. Poorly functioning items were removed, and the model was refit to create the final questionnaire. RESULTS: The psychometrically validated PROs measure was reduced to a 59-item questionnaire measuring 7 unidimesnional domains: central vision, color vision, contrast sensitivity, scotopic function, photopic peripheral vision, mesopic peripheral vision, and photosensitivity. A total of 39 items were removed because of poor factor loading, low item information, poor person-ability differentiation, or high item-level interdependence. This novel questionnaire produces a reliable domain score for person ability that does not show significant test-retest variability across repeated administration. CONCLUSIONS: The final PRO questionnaire, known as the Michigan Retinal Degeneration Questionnaire, is psychometrically validated and available for use in the evaluation of patients with inherited retinal degenerations.

The Michigan Vision-Related Anxiety Questionnaire: A Psychosocial Outcomes Measure for Inherited Retinal Degenerations.

OBJECTIVE: We sought to construct and validate a patient-reported outcome measure for screening and monitoring vision-related anxiety in patients with inherited retinal degenerations. DESIGN: Item-response theory and graded response modeling to quantitatively validate questionnaire items generated from qualitative interviews and patient feedback. METHODS: Patients at the Kellogg Eye Center (University of Michigan, Ann Arbor, Michigan, USA) with a clinical diagnosis of an inherited retinal degeneration (n = 128) participated in an interviewer-administered questionnaire. The questionnaire consisted of 166 items, 26 of which pertained to concepts of "worry" and "anxiety." The subset of vision-related anxiety questions was analyzed by a graded response model using the Cai Metropolis-Hastings Robbins-Monro algorithm in the R software mirt package. Item reduction was performed based on item fit, item information, and item discriminability. To assess test-retest variability, 25 participants completed the questionnaire a second time 4 to 16 days later. RESULTS: The final questionnaire consisted of 14 items divided into 2 unidimensional domains: rod function anxiety and cone function anxiety. The questionnaire exhibited convergent validity with the Patient Health Questionnaire for symptoms of depression and anxiety. This vision-related anxiety questionnaire has high marginal reliability (0.81 for rod-function anxiety, 0.83 for cone-function anxiety) and exhibits minimal test-retest variability (ρ = 0.81 [0.64-0.91] for rod-function anxiety and ρ = 0.83 [0.68-0.92] for cone-function anxiety). CONCLUSIONS: The Michigan Vision-Related Anxiety Questionnaire is a psychometrically validated 14-item patient-reported outcome measure to be used as a psychosocial screening and monitoring tool for patients with inherited retinal degenerations. It can be used in therapeutic clinical trials for measuring the benefit of an investigational therapy on a patient's vision-related anxiety.

Density-based classification in diabetic retinopathy through thickness of retinal layers from optical coherence tomography.

Diabetic retinopathy (DR) is a severe retinal disorder that can lead to vision loss, however, its underlying mechanism has not been fully understood. Previous studies have taken advantage of Optical Coherence Tomography (OCT) and shown that the thickness of individual retinal layers are affected in patients with DR. However, most studies analyzed the thickness by calculating summary statistics from retinal thickness maps of the macula region. This study aims to apply a density function-based statistical framework to the thickness data obtained through OCT, and to compare the predictive power of various retinal layers to assess the severity of DR. We used a prototype data set of 107 subjects which are comprised of 38 non-proliferative DR (NPDR), 28 without DR (NoDR), and 41 controls. Based on the thickness profiles, we constructed novel features which capture the variation in the distribution of the pixel-wise retinal layer thicknesses from OCT. We quantified the predictive power of each of the retinal layers to distinguish between all three pairwise comparisons of the severity in DR (NoDR vs NPDR, controls vs NPDR, and controls vs NoDR). When applied to this preliminary DR data set, our density-based method demonstrated better predictive results compared with simple summary statistics. Furthermore, our results indicate considerable differences in retinal layer structuring based on the severity of DR. We found that: (a) the outer plexiform layer is the most discriminative layer for classifying NoDR vs NPDR; (b) the outer plexiform, inner nuclear and ganglion cell layers are the strongest biomarkers for discriminating controls from NPDR; and (c) the inner nuclear layer distinguishes best between controls and NoDR.

Content generation for patient-reported outcome measures for retinal degeneration therapeutic trials.

PURPOSE: Generate content for a patient-reported outcome (PRO) measure for use in future clinical trials for inherited retinal degenerations. METHODS: Patients at the University of Michigan Kellogg Eye Center with a clinical diagnosis of inherited retinal degeneration with varying phenotypes were recruited for interviews. First, in-depth interviews were performed to solicit a wide range of patient experiences pertaining to visual function. Coders qualitatively analyzed the transcripts from these interviews using Atlas.ti software (Version 8.1.3 (522)) to draft questionnaire items. Next, the questionnaire was tested and refined based on participant feedback in cognitive interviews and administrator feedback in the pilot survey administration (pilot interviews). RESULTS: A total of 55 participants with a clinical diagnosis of inherited retinal degeneration were interviewed throughout the three study phases: in-depth interviews (n = 26), cognitive interviews (n = 16), and pilot interviews (n = 13). Coded items were analyzed for frequency of occurrence and related themes, then organized into common domains. Within each domain, PRO items were drafted to address the functional limitations or adaptations experienced by patients. CONCLUSIONS: Items for a PRO measure have been drafted and evaluated for interpretability in the target inherited retinal degeneration patient population. Content validity for the items was established through a process of in-depth interviews, cognitive interviews, and pilot interviews.

Patient-reported outcome measures in inherited retinal degeneration gene therapy trials.

Patient-reported outcome (PRO) measures have the potential to uniquely capture patient experience and serve as an outcome measure in inherited retinal degeneration (IRD) gene therapy trials. An IRD-specific patient-reported outcome measure may yield valuable information that has not been obtained from inherited retinal dystrophy gene therapy trials published to-date. Existing PRO measures have inherent limitations for use in IRD gene therapy trials. Developing an applicable patient-reported outcome measure for such trials needs to incorporate patient input from the target population, demonstrate sound psychometric properties, and be made in accordance with U.S. Food and Drug Administration (FDA) guidelines. This review will discuss the currently available PRO instruments, their limitations for IRD therapeutic trials, and suggestions for future PRO development in IRD populations. The PRO instruments highlighted were identified in PubMed search of English-language journals and previously published review articles.

The Effect of Glycemia on Choroidal Thickness in Different Stages of Diabetic Retinopathy.

OBJECTIVE: The purpose of this study was to evaluate the influence of renal and glycemic parameters on choroidal thickness (CT) in patients with diabetes with and without diabetic retinopathy (DR). METHODS: This cross-sectional study included patients with and without diabetes. Patients underwent comprehensive ocular examination. CT was obtained using spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) mode. Clinical parameters were body mass index, mean arterial pressure, glycated hemoglobin, fasting plasma glucose, estimated glomerular filtration rate, and capillary plasma glucose (CPG) a few minutes before EDI-SD-OCT. RESULTS: The study included 275 participants: 42 with diabetes and no DR, 43 with mild nonproliferative diabetic retinopathy (NPDR), 46 with moderate NPDR, 39 with severe NPDR, 24 with proliferative diabetic retinopathy (PDR), 40 with previous panretinal photocoagulation (PRP) treatment for DR, and 41 without diabetes. The diabetic patients had thinner subfoveal CT than the nondiabetic participants (280.5 ± 83.4 vs. 327.1 ± 48.8 µm, p < 0.001). After multivariable adjustment, CT was significantly correlated with age, DR stage, and CPG. In patients with mild and moderate NPDR, a higher level of CPG was associated with thicker CT. This relationship was not found in patients with PDR. CONCLUSION: CPG had the strongest correlation with CT in patients with NPDR (mild, moderate, and severe), but not in PDR and PRP PDR patients. Our study suggests that the glucose level at the time of the test should be aggregated to other systemic and ocular parameters, such as age and axial length, when studying the choroid using SD-OCT.

Comparison of Fundus-Guided Microperimetry and Multifocal Electroretinography for Evaluating Hydroxychloroquine Maculopathy.

PURPOSE: To compare retinal function by using fundus-guided microperimetry (MP) and multifocal electroretinography (mfERG) for detecting hydroxychloroquine (HCQ) maculopathy. METHODS: Forty-six eyes of 25 patients referred to our clinical practice for HCQ maculopathy assessment and 3 groups of normal control subjects were evaluated by mfERG and MP. Macular structure was assessed using spectral-domain optical coherence tomography (SD-OCT). Ring ratios from the three innermost mERG rings were compared with average sensitivity of each MP ring at approximately equivalent distances from the fovea. HCQ toxicity was defined as an mfERG ring ratio or mean MP ring sensitivity >2 standard deviations below the normal mean. The sensitivity and specificity of MP to detect HCQ toxicity relative to mfERG were evaluated. RESULTS: MP rings MR2 and MR3 were positively correlated with corresponding mfERG ring ratios (r = 0.52, P = 0.002 and r = 0.56, P < 0.001 respectively). Ring 2 and ring 3 measures of MP and mfERG were significantly worse in HCQ eyes than controls (P < 0.001). The sensitivity of MP to detect toxicity for MR1 through MR3 ranged from 33% to 88%, whereas specificity ranged from 72% to 85%. Through rings 1 to 3, the frequency of abnormal function ranged from 20% to 48% for MP, 11% to 35% for mfERG, and 41% to 45% for SD-OCT. CONCLUSIONS: The frequency of detection of HCQ toxicity with MP was greater than with mfERG. MP showed an overall good sensitivity and moderate specificity in detecting HCQ-induced functional deficits. TRANSLATIONAL RELEVANCE: Results from this study may allow clinicians to improve screening accuracy for HCQ toxicity by using the alternative modality of MP.

Prospective evaluation of intravitreal bevacizumab for ischemic central retinal vein occlusion.

BACKGROUND: Although previous studies have evaluated the effect of anti-VEGF therapies for central retinal vein occlusion (CRVO) patients, the majority of previous studies have excluded or included a very small number of patients with ischemic CRVO (iCRVO). The aim of our study is to examine the effects of bevacizumab on macular edema secondary to ischemic central retinal vein occlusion, as well as the effects on central choroidal thickness and best-corrected visual acuity. METHODS: In this prospective, interventional case series, iCRVO was defined by the presence of ≥ 10 or more disc diameter areas of retinal nonperfusion by fluorescein angiography (FA) and by the presence of a b/a ratio less than 1.5 by full-field electroretinogram (ffERG). Nine eyes with iCRVO received monthly bevacizumab 0.5 mg injections at baseline and months 1 to 5 for a maximum of six injections. Main outcome measures were visual acuity (Snellen), central foveal thickness, and central choroidal thickness as measured by Spectral-Domain Optical Coherence Tomography (SD-OCT) at baseline and at 6 month following initial intravitreal bevacizumab injection. Pairwise t-tests and the Wilcoxon signed-rank test were conducted to compare the outcome measures. RESULTS: After intravitreal administration of bevacizumab, there was a significant reduction of central foveal thickness from 858 ± 311 µm at baseline to 243 ± 106 µm at the 6-month follow-up, as well as a significant reduction of central choroidal thickness from 282 ± 38 µm at baseline to 227 ± 56 µm at the 6-month follow-up (p = 0.0006, p = 0.0003 respectively). The visual acuity worsened from a median of 1.3 to 1.7 (p = 0.02). CONCLUSION: In patients with iCRVO, intravitreal bevacizumab led to a reduction of central macular edema and central choroidal thickness, but a worsening of visual acuity. Intravitreal bevacizumab reduces macular edema but is not able to overcome the poor prognosis of iCRVO.

Macular hyperpigmentary changes in ABCA4-Stargardt disease.

BACKGROUND: Stargardt disease (STGD) and age-related macular degeneration (AMD) share clinical and pathophysiological features. In AMD, macular hyperpigmentary changes are associated to a worse prognosis. The purpose of this study was to characterize macular hyperpigmentary changes in patients with STGD and associate them with the severity of phenotype. MATERIALS AND METHODS: This retrospective cross-sectional study included 141 patients with STGD. Hyperpigmentary changes were evaluated on color fundus photography and spectral-domain optical coherence tomography. Severity of phenotype was assessed by full-field electroretinogram (ffERG) and fundus autofluorescence (FAF) patterns, and visual acuity (VA). RESULTS: Thirty patients (21.7%) showed macular hyperpigmentary changes in four distinct patterns. Out of seventeen patients who had follow-up images, eleven patients demonstrated increases of the hyperpigmented lesions, and progression of the underlying RPE atrophy overtime. VA remained stable. Of 28 patients who had ffERG, 17 patients presented with reduction of photopic and scotopic responses, while 8 presented with reduction of photopic responses only, and 3 presented with preserved photopic and scotopic responses. Of 25 patients who had FAF available, 12 presented with widespread disease extending anteriorly to the vascular arcades, while eight presented with widespread disease, extending beyond the vascular arcades, and 5 presented with disease confined to the foveal area. CONCLUSION: In this study, we demonstrated that patients with STGD with macular hyperpigmented lesions had a severe phenotype. Overtime, hyperpigmented lesions increased in size, spread across the retina, and migrated to different retinal layers. Macular hyperpigmentation may be a marker of advanced stage of the disease.

Contrast sensitivity deficits in patients with mutation-proven inherited retinal degenerations.

BACKGROUND: Patients with retinal diseases frequently complain of poor visual function even when visual acuity is relatively unaffected. This clinical finding has been attributed to deficits in contrast sensitivity (CS). The purpose of our study was to evaluate the CS in patients with clinical and genetic diagnosis of inherited retinal degeneration (IRD) and relatively preserved visual acuity. METHODS: Seventeen patients (30 eyes) with IRD and visual acuity of 20/40 or better, and 18 controls (18 eyes) without any ocular condition underwent slit lamp examination, visual acuity testing via standard Snellen chart testing, CS testing via the Quick Contrast Sensitivity Function (QCSF), and Spectral Domain Optical Coherence Tomography (SD-OCT). CS were measured at 1.0, 1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree (cpd). T tests with general estimated equations were used to compare CS between groups. Wald chi square followed by pairwise comparisons was used to compare CS between multiple groups. RESULTS: We included 12 patients with rod-cone dystrophy (RCD), 3 patients with Stargardt disease (STGD) and 2 patients with Best disease. Patients with IRD had significantly worse CS than controls (p < 0.001) in all spatial frequencies. Patients with STGD had more marked deficits in CS than patients with Best disease (p < 0.001) and RCD (p < 0.001) despite having similar visual acuities. CONCLUSION: Patients with IRD, especially patients with STGD with relatively preserved visual acuity have marked deficits in CS when measured across a range of spatial frequencies. We recommend that clinical trials for STGD incorporate CS measured over a range of spatial frequencies as a secondary clinical endpoint for monitoring visual function. CS may provide an explanation for complaints of visual dysfunction when visual acuity is not significantly altered.