ASSOCIATION OF ORAL MONTELUKAST WITH REDUCED ODDS OF DEVELOPING EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: This study was conducted to evaluate the association of oral montelukast, selective antagonism for cysteinyl leukotriene receptor 1, with reduced odds of exudative age-related macular degeneration (exAMD) development. METHODS: This case-control study was conducted using institutional cohort finder tool, and included 1913 patients with exAMD (ICD: H35.32 and 362.52) and 1913 age- and gender-matched control subjects without exAMD. Subanalysis among 1913 exAMD and 324 nonexudative AMD was also conducted. RESULTS: A total of 47 (2.5%) exAMD cases were identified to have a history of oral montelukast use before exAMD diagnosis, compared with 84 (4.4%) controls. Montelukast usage was significantly associated with reduced odds of exAMD in the multivariable analysis (adjusted odds ratio [OR]: 0.50, 95% confidence interval: 0.31-0.80) and nonsteroidal anti-inflammatory drug usage (adjusted OR: 0.69). Caucasian race, history of smoking, and nonexudative macular degeneration in either eye were also found to have a significant relationship with increased odds of exAMD. In the subanalysis, montelukast usage showed significant association with reduced odds of developing exAMD from nonexudative AMD (adjusted OR: 0.53, 95% confidence interval: 0.29-0.97) and the presence of atopic disease (adjusted OR: 0.60). CONCLUSION: The study results suggested that oral montelukast is linked to reduced odds of exAMD development.

Longitudinal Comparative Analysis of Semi-Automated Aqueous Flare Measurements with Clinical Grading and Visual Outcomes in Uveitic Eyes.

PURPOSE: To evaluate the correlation between longitudinal changes in aqueous flare measured by laser flare photometer (LFP), best-corrected visual acuity (BCVA), and clinical grade using both Standardization of Uveitis Nomenclature (SUN) and modified SUN (MSUN) scales uveitis patients. METHODS: Patients were classified according to both SUN and MSUN grading scales. LFP measurements were acquired (Kowa FM-700) at each visit. Mean change in LFP was assessed longitudinally, comparing with those in visual acuity, SUN, and MSUN grading scales. RESULTS: Mean change in LFP was correlated to those in BCVA (p = .018), SUN scale (p < .001), and MSUN scale (p = .008). Cases within same initial SUN (0 and 1+) and MSUN (0.5+ and 1+) grades and different longitudinal flare prognosis (decreased/unchanged/increased) had significantly different initial LFP values (all p < .05). CONCLUSIONS: LFP measurement is beneficial in monitoring inflammatory activity. Cases of identical clinical flare scores with different clinical prognosis may be predicted by LFP.

Efficacy and Safety of Tocilizumab in the Management of Non-Infectious Uveitis Failed with Conventional Immunomodulatory and Anti-TNFα Therapies.

PURPOSE: To determine the outcomes of intravenous (IV) tocilizumab (TCZ) in patients with non-infectious uveitis who failed with conventional immunomodulatory and anti-TNFα therapies. METHODS: Records of seven patients with non-infectious uveitis treated with monthly IV TCZ (4-10 mg/kg) or biweekly IV TCZ (8 mg/kg) were reviewed. Outcome measures were changes in visual acuity, anterior chamber cell and flare grade, vitreous haze, central subfield thickness (CST), and fluorescein angiography (FA) score. RESULTS: Ten eyes of seven patients received TCZ therapy. Median age of patients was 14 (range, 7-24) years. Median duration of TCZ therapy was 15 (range, 5-32) months. Mean CST reduced from 373 ± 101.0 µm to 298.2 ± 40.3 µm. Mean FA score reduced from 12.5 ± 4.3 to 3.6 ± 2.6. One patient developed elevated liver transaminases. CONCLUSION: IV TCZ is a potentially effective and safe therapeutic option for the management of refractory non-infectious uveitis.

Proteomic analysis of autoimmune retinopathy implicates NrCAM as a potential biomarker.

Purpose: To identify vitreous molecular biomarkers associated with autoimmune retinopathy (AIR). Design: Case-control study. Participants: We analyzed six eyes from four patients diagnosed with AIR and eight comparative controls diagnosed with idiopathic macular holes and epiretinal membranes. Methods: Vitreous biopsies were collected from the participants and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) or multiplex ELISA. Outcome Measures: Protein expression changes were evaluated by 1-way ANOVA (significant p-value <0.05), hierarchical clustering, and pathway analysis to identify candidate protein biomarkers. Results: There were 16 significantly upregulated and 17 significantly downregulated proteins in the vitreous of three AIR patients compared to controls. The most significantly upregulated proteins included lysozyme C (LYSC), zinc-alpha-2-glycoprotein (ZA2G), complement factor D (CFAD), transforming growth factor-beta induced protein (BGH3), beta-crystallin B2, and alpha-crystallin A chain. The most significantly downregulated proteins included disco-interacting protein 2 homolog (DIP2C), retbindin (RTBDN), and amyloid beta precursor like protein 2 (APLP2). Pathway analysis revealed that vascular endothelial growth factor (VEGF) signaling was a top represented pathway in the vitreous of AIR patients compared to controls. In comparison to a different cohort of three AIR patients analyzed by multiplex ELISA, a commonly differentially expressed protein was neuronal cell adhesion molecule (NrCAM) with p-values of 0.027 in the LC-MS/MS dataset and 0.035 in the ELISA dataset. Conclusion: Protein biomarkers such as NrCAM in the vitreous may eventually help diagnose AIR.

Two Phase 3 Studies on Ophthalmologic Effects of Roxadustat Versus Darbepoetin.

Introduction: Roxadustat is an orally administered hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that represents a novel therapeutic option for patients with anemia of chronic kidney disease (CKD). Methods: Conducted in Japan, CL-0307 (NCT02952092) and CL-310 (NCT02988973) were phase 3, darbepoetin alfa (DA)-controlled studies conducted in dialysis-dependent (DD) and non-DD (NDD) patients with CKD, respectively, where patients were randomized to receive roxadustat or DA. Ophthalmic imaging and assessments of visual acuity were performed up to week 24 or at study discontinuation. Ophthalmic imaging was centrally evaluated by independent readers masked to the study treatment. Results: In CL-0307, 302 patients (roxadustat, n = 150; DA, n = 152) received ≥1 dose of the study drug and were included in this analysis. In CL-0310, 262 patients (roxadustat, n = 131; DA, n = 131) received ≥1 dose of the study drug and were included in this analysis. Proportions of DD patients with new or worsening retinal hemorrhages (RHs) in the roxadustat group and DA group were 32.4% (46 of 142) and 36.6% (53 of 145), respectively. Proportions of NDD patients with CKD with new or worsening RH in the roxadustat and DA groups were 31.4% (38 of 121) and 39.8% (51 of 128), respectively. Similar trends were apparent in subgroup analyses: patients with/without RH at baseline and with/without diabetes mellitus at baseline. In both studies, there were no differences in retinal thickness, visual acuity, presence of hard exudates or cotton wool spots, or presence of intra- and subretinal fluid between groups, at any given time point. Conclusion: In these studies, roxadustat, compared with DA, was not associated with an increased risk of adverse ophthalmologic events in these cohorts.

Correlation of Clinical Aqueous Flare Grading to Semi-Automated Flare Measurements Using Laser Flare Photometry.

PURPOSE: To compare laser flare photometry (LFP) measurements of aqueous flare with Standardization of Uveitis Nomenclature (SUN) and modified SUN grading. METHODS: In this prospective study with multicenter design, uveitis patients were classified according to SUN and modified SUN grading scales. LFP was performed with Kowa FM-700 flaremeter. Mean LFP values were compared with SUN and MSUN scores. RESULTS: The study included 475 LFP measurements, of which 216, 48, 150, 31, 28 and 2 had 0, 0.5+, 1+, 1.5+, 2+ and 3+ flare, respectively. LFP values were significantly different between each two consecutive steps for both clinical gradings (all P < .05). Cut-off values for modified SUN grading steps were defined as 5.7, 9.7, 15.7 and 43.2 for 0/0.5+, 0.5+/ 1+, 1+/1.5+ and 1.5/2+ borders of clinical flare, respectively. CONCLUSIONS: LFP proves to be an objective measurement in analyzing aqueous flare comparable to both SUN and MSUN clinical grading systems.

Effect of Fundus Fluorescein Angiography on Semiautomated Aqueous Flare Measurements.

PURPOSE: To evaluate the effects of fluorescein fundus angiography (FFA) on semiautomated aqueous flare measurements. METHODS: Laser flare photometer (LFP) measurements was performed at baseline, 30 min, and 4 h after the intravenous administration of sodium fluorescein dye. FFA was performed immediately after the baseline LFP measurement. LFP values at 30 min and 4 h after FFA were compared to baseline values. Mean change in LFP measurements at 30 min and 4 hafter baseline was compared between FFA arm and controls. RESULTS: The mean flare measurement in the FFA and control arm dropped 6% (p value = 0.002) and 9% (p value = 0.04), respectively. Mean change in LFP measurement at 30 min and 4 h after baseline was not significant between FFA arm and controls. CONCLUSIONS: Administration of fluorescein dye does not increase LFP values. The decrease in the LFP measurement following FFA may be attributed to dilation drops.

Effect of light backscattering from anterior segment structures on automated flare meter measurements.

BACKGROUND: To evaluate effect of maximal anterior cortical lens density, iris scatter and anterior chamber depth on laser flare photometry. METHODS: Patients diagnosed with clinical uveitis were enrolled in the study. Clinical flare gradings were recorded upon the Standardization of Uveitis Nomenclature. Aqueous flare was measured with an automated device (Kowa FM-700). Back-scattering from anterior cortical lens and anterior iris surface was calculated from Scheimpflug images. A curvilinear regression model was used to calculate estimated values for each clinical grade. These values were used to split cases in Group I (laser flare photometry lower than estimated) and Group II (laser flare photometry higher than estimated). Mean anterior chamber depth, pupil aperture, maximal anterior cortical lens density and iris scatter values were compared between two groups. A stepwise multiple regression analysis was performed to determine the effect of clinical flare gradings and ocular parameters on aqueous flare measurements. RESULTS: The study included 228 eyes of 114 cases. Scheimpflug images were obtained from 105 eyes. Estimated aqueous flare measurements (in photons/milliseconds) were 4.87, 8.50, 14.81, 25.83, 45.04 and 136.93 for 0, 0.5+, 1+, 1.5+, 2+ and 3+ clinical flare respectively. Group II had higher maximal anterior cortical lens density than Group I (96.6 ± 37.1 vs 77.9 ± 17.1 pixel unit, p = 0.001). The measured aqueous flare was significantly related to clinical flare, maximal anterior cortical lens density and pupil aperture (adjusted R2: 0.480, p < 0.001). CONCLUSION: The back-scattered light from anterior cortical lens could affect laser flare photometry measurements. This effect might be quantified by Scheimpflug imaging.

Distinct Patterns of Choroidal Lesions in Punctate Inner Choroidopathy and Multifocal Choroiditis Determined by Heatmap Analysis.

PURPOSE: A heatmap analysis of choroidal lesions in patients with punctate inner choroidopathy (PIC) or multifocal choroiditis (MFC) with or without uveitis was performed to determine if there were any distinguishing features among these uveitic entities. METHODS: Retrospective review of medical records was conducted at the Byers Eye Institute, Stanford. Fundus photographs were masked and placed on a standardized template. Lesions were identified and heatmaps were generated in a standardized fashion. RESULTS: 30 eyes were identified with PIC or MFC. Heatmap analysis revealed three distinct patterns of fundus lesions: posterior, peripheral, and combined. All patients with PIC had the posterior pattern. Patients with MFC had the peripheral or combined pattern, and all patients with MFC with uveitis had the combined pattern. CONCLUSION: Three patterns of fundus lesions were identified in patients with PIC and MFC. PIC and MFC may represent two separate disease entities with distinct phenotypes of choroidal lesions.

Phase 1b Randomized Controlled Study of Short Course Topical Recombinant Human Nerve Growth Factor (rhNGF) for Neuroenhancement in Glaucoma: Safety, Tolerability, and Efficacy Measure Outcomes.

PURPOSE: No approved therapies directly target retinal ganglion cells (RGCs) for neuroprotection or neuroenhancement in glaucoma. Recombinant human nerve growth factor (rhNGF) has been shown to promote RGC survival and function in animal models of optic neuropathy. Here we evaluate the safety, tolerability, and efficacy of short-term, high-dose rhNGF eye drops versus placebo in a cohort of glaucoma patients. DESIGN: This was a prospective, phase 1b, single-center, randomized, double-masked, vehicle-controlled, parallel-group study. METHODS: This study was designed to assess safety and tolerability as well as short-term neuroenhancement of structure and function (clinicaltrials.gov NCT02855450). A total of 60 open-angle glaucoma patients were randomized 40:20 to receive either 180 µg/mL rhNGF or vehicle control eye drops in both eyes, 3 times daily for 8 weeks, with a 24-week post-treatment follow-up. One eye was officially selected as the study eye, although both eyes were studied and dosed. Primary endpoints were safety, as assessed by adverse events, and tolerability, as assessed by patient-reported outcomes. Secondary outcome measures included best corrected visual acuity (BCVA), Humphrey visual field, electroretinograpy (ERG), and optical coherence tomography (OCT) of retinal nerve fiber layer (RNFL) thickness at baseline, after 8 weeks of treatment, and at 4 and 24 weeks after treatment (12 and 32 weeks total). RESULTS: Of the 60 randomized patients, 23 were female (38%) and the average age was 66.1 years. Through week 32, there were no treatment-related serious adverse events, including no unexpectedly severe progression of optic neuropathy, no adverse events affecting ocular function or pressure, and no drug-related systemic toxicity. Topical high-dose rhNGF was tolerated well, with a low level of symptom burden mainly eliciting periocular ache (in 52% of treated group and 5% of placebo group) and only 3 patients (7.5%) discontinuing treatment because of discomfort, of whom 1 patient (2.5%) prematurely withdrew from the study. There were no statistically significant differences in global indices of Humphrey visual field and no meaningful differences in total, quadrant, or clock-hour mean RNFL thickness between the groups, although both of these function and structure measures showed nonsignificant trends toward significance in favor of rhNGF. Real-world participant data was used to generate an estimate of cohort size needed to power subsequent studies. CONCLUSIONS: Use of rhNGF is safe and tolerable in a topical 180-µg/mL formulation. Although no statistically significant short-term neuroenhancement was detected in this trial, given the strong effects of NGF in preclinical models and the trends detected in this study, analysis for efficacy in a neuroprotection trial is warranted. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Evaluating optical coherence tomography (OCT) findings as potential biomarkers in central nervous system (CNS) lymphoma with or without ocular involvement.

BACKGROUND: To evaluate spectral domain optical coherence tomography (SD-OCT) findings as biomarkers in primary central nervous system lymphoma (PCNSL) with or without ocular involvement. METHODS: This study was a cross-sectional study and patients with a confirmed diagnosis of PCNSL with or without ocular involvement were included. Patient cohort finder tool was used to identify patients with lymphoma using ICD-10 codes (C82-C88), from January 2004 to October 2017. A total of 14,820 patients were identified. Procedure code (92134) for optical coherence tomography (OCT) was then applied to identify patients who had underdone OCT imaging at ophthalmology clinic. Clinic charts of 460 patients with lymphoma and available OCT were reviewed to identify patients with confirmed diagnosis of PCNSL and divided into two groups (Group 1: with and Group 2: without ocular involvement). OCT scans of patients in both study groups were analyzed for the presence of (1) Hyperreflective deposits in choroid, retinal pigment epithelium (RPE), outer and inner retina; (2) RPE thickening; (3) Vitreous debris; (4) Intraretinal fluid; (5) Ellipsoid zone disruption by masked graders. Chi-square was used to analyze the difference between the groups. RESULTS: Twenty-two eyes (11 patients) with PCNSL were included this study (Group 1: 6 eyes and Group 2: 16 eyes). Mean age of subjects was 65 years. Five patients (45.45%) were female. There was no statistically significant difference between the groups for the presence of hyperreflective deposits in choroid, RPE, outer and inner retina, and presence of RPE thickening, intraretinal fluid, and ellipsoid zone disruption. Vitreous debris was found more commonly in group 1 subjects (83%) than group 2 (31.25%) (p = 0.029). All subjects in both groups showed hyperreflective deposits in the RPE demonstrating RPE infiltration. However, RPE thickening was noted only in 3 patients (Group1: 1 and Group2: 2). CONCLUSIONS: OCT finding of hyperreflective deposits present in eyes with lymphoma secondary to PCNSL are also observed in eyes with PCNSL without ocular disease. However, the vitreous deposits are more commonly found in eyes with ocular disease. These hyperreflective deposits can serve as biomarkers for early detection of ocular involvement by PCNSL.

Current concepts in the diagnosis and management of antiphospholipid syndrome and ocular manifestations.

Antiphospholipid syndrome (APS) is an autoimmune disorder associated with obstetrical complications, thrombotic complications involving both arteries and veins, and non-thrombotic manifestations affecting multiple other systems presenting in various clinical forms. Diagnosis requires the presence of antiphospholipid antibodies. The exact pathogenesis of APS is not fully known. However, it has recently been shown that activation of different types of cells by antiphospholipid antibodies plays an important role in thrombosis formation. Ocular involvement is one of the important clinical manifestations of APS and can vary in presentations. Therefore, as an ophthalmologist, it is crucial to be familiar with the ocular findings of APS to prevent further complications that can develop. Furthermore, the ongoing identification of new and specific factors contributing to the pathogenesis of APS may provide new therapeutic options in the management of the disease in the future.

Eye trauma in falls presenting to the emergency department from 2006 through 2015.

AIMS: To characterise the epidemiology of eye trauma in the event of falls presenting to the emergency departments (ED) in the USA. METHOD: Retrospective cohort study. Nationwide Emergency Department Sample was used to analyse fall encounters presenting to the ED with eye trauma from 2006 to 2015. National estimates of the leading diagnoses were determined, and multivariable regression was used to determine the relationship between factors involved in fall encounters presenting with eye trauma. RESULTS: From 2006 to 2015, an estimated 87 991 036 fall encounters presented to the ED, of which 952 781 encounters had eye trauma as either a primary or secondary diagnosis. The overall incidence of fall encounters with eye trauma per 100 000 US population increased from 30.7 encounters in 2006 to 33.8 encounters per 100 000 population in 2014 with a decrease seen in 2015. Eye trauma, including vision-threatening type, was highest in females (n=500 520, 52.5%), elderly (n=400 209, 42%) and children (n=2 06 741, 21.7%). Elderly were more likely to have eye trauma in the setting of falls (adjusted OR (aOR) 2.06, 95% CI 2.02 to 2.11) and be admitted (aOR 1.89, 95% CI 1.86 to 1.91) than adults (reference). The leading types of eye trauma were contusion of orbital tissues (n=174 292, 18.3%), laceration of eyelid and periocular area (n=172 361, 18.1%) and orbital fractures (n=151 013, 15.8%). CONCLUSIONS: Falls are preventable, yet the incidence of falls and resulting eye trauma are increasing despite our best efforts. As ophthalmologists, we should not only develop guidelines to recognise and counsel at-risk groups under our care but also strategies for prevention of eye trauma secondary to falls.

Posterior segment inflammatory outcomes assessed using fluorescein angiography in the STOP-UVEITIS study.

BACKGROUND: Although fluorescein angiography (FA) is a frequently used imaging modality in patients with non-infectious uveitis (NIU), it has not been reliably used for objective assessment of posterior segment inflammatory outcomes in these patients. In this index study we report the posterior segment inflammatory outcomes of two different doses of intravenous (IV) infusions of tocilizumab (TCZ), an IL-6 inhibitor, in eyes with NIU using a semi-quantitative FA scoring system. METHODS: STOP-Uveitis is a randomized, multi-center clinical trial conducted at 5 clinical centers across the United States. The study evaluated the role of TCZ in patients with NIU. Thirty-seven (37) patients with NIU were randomized into one of two treatment groups in a ratio of 1:1. Group 1 received IV infusions of 4 mg/kg TCZ and group 2 received IV infusions of 8 mg/kg TCZ. Infusions were given every 4 weeks in both groups until month 6 (primary endpoint). Posterior segment inflammatory outcomes were assessed by evaluating FA at baseline and month 6 by graders at a central reading center. A previously reported, semi-quantitative, scoring system for FA was used to assess signs that represent ongoing inflammatory processes in the posterior segment. These signs included optic disc hyperfluorescence, macular edema, retinal vascular staining and/or leakage, capillary leakage, retinal capillary nonperfusion, neovascularization of the optic disc, neovascularization elsewhere, pinpoint leaks, and retinal staining and/or subretinal pooling. Statistical significance was set at p < 0.05. Main outcome measures included change in posterior segment inflammation as assessed using FA at month 6. RESULTS: 37 eyes (37 patients) were randomized in the STOP-Uveitis study. 30 eyes were found to be eligible for this sub-study based on study criteria. Seven eyes had ungradable images at either baseline or month 6 and were therefore excluded from the analysis. The reduction in FA inflammatory scores at month 6 were statistically significant in both groups (p < 0.05). The difference between the two groups was not significant (p = 0.351). CONCLUSIONS: IV infusions of tocilizumab (both 4 and 8 mg/kg) are effective in improving posterior segment inflammation in eyes with NIU. A semi-quantitative FA scoring system may be used as a reliable outcome measure for assessment of posterior segment inflammation.ClinicalTrials.gov Identifier: NCT01717170.

Pharmacological agents in development for diabetic macular edema.

BACKGROUND: Diabetic macular edema (DME) is the leading cause of visual loss in patients with diabetic retinopathy. There has been a paradigm shift in the treatment of DME since the advent of anti-vascular endothelial growth factor (anti-VEGF) therapy. The safety and efficacy of anti-VEGF therapy has been well established. Although efficacious, currently approved anti-VEGF agents are associated with certain limitations, which include, among others: frequent need for injections, high treatment cost and variable response to treatment. These challenges have led to an active search for more novel agents that may be able to overcome these limitations. AREAS COVERED: The index review focuses on novel treatment agents that target various pathways in patients with DME. These agents are used either as monotherapy or in combination with other agents in the management of DME. Drugs discussed include novel anti-VEGF inhibitors, TIE-2 receptor modulators, integrin peptide inhibitors, rho kinase inhibitors, and future therapies such as neuroprotection and gene therapy. CONCLUSIONS: The future of investigational pharmacological therapy appears promising for patients with DME. Results from early clinical trials indicate that newer agents highlighted in the study may be safe and efficacious treatment options for patients with DME. However, data from large multicenter clinical trials need to be analyzed before these agents can be incorporated into clinical practice.

Yet another case of ocular sarcoidosis.

PURPOSE: To report a case of bilateral pan-uveitis resembling fungal and viral endophthalmitis in a patient who was ultimately diagnosed with sarcoidosis. OBSERVATION: A 64-year-old female presented with a four-day history of painless vision loss in the right eye. She presented with multiple concurrent systemic complaints, including a history of oral and genital sores, patches of hypopigmented skin on her forearms, and occasional shortness of breath. Upon further examination, she was noted to have bilateral pan-uveitis, which was more severe in the right than left eye. Posterior pole examination of the right eye revealed dense vitritis with multiple large whitish round balls that seemed suggestive of fungal or viral endophthalmitis. Initial therapies included intravitreal (IVT) foscarnet and intravenous (IV) acyclovir, followed by IV amphotericin B and oral voriconazole, which did not improve ocular signs and symptoms. Further evaluations ruled out infectious etiologies and lymphoma. Chest computerized tomography (CT) scan revealed findings suggestive of sarcoidosis, which was confirmed with lung biopsy. Anti-viral and -fungal treatments were discontinued, and the patient was started on IV methylprednisolone followed by oral prednisone and mycophenolate mofetil. Ocular symptoms improved, and the patient remained stable after treatment. CONCLUSION AND IMPORTANCE: The index report illustrates a case of ocular sarcoidosis that imitated the presentation of infectious endophthalmitis. Though ocular sarcoidosis is known to masquerade as a range of disorders and constitutes part of the differential diagnosis for infectious endophthalmitis, sarcoidosis has not been reported in recent literature to imitate the presentation of fungal endophthalmitis. The index case suggests that ocular sarcoidosis should be considered in the differential diagnoses of fungal endophthalmitis.

Correction of perceived visual distortions using a software application and correlation to age-related macular degeneration.

PURPOSE: To investigate the use of software-generated corrections in neutralizing perceived distortions in age-related macular degeneration. METHODS: A tablet-based application was utilized to elicit distortions. Five subjects (seven eyes: neovascular age-related macular degeneration and three eyes: non-neovascular age-related macular degeneration) traced the reference lines, and their distortion traces were recorded. To counter distortion, a software-generated trace was re-traced by subjects to produce a corrected trace. Final traces were superimposed on optical coherence tomography images and following distances calculated: (a) dDT: distance between distortion trace and reference line; (b) dGT: distance between software-generated trace and corrected trace; (c) dCT: distance between corrected trace and reference line. Mean percent improvement in distortion was reported. Mean effectiveness of correction was also reported by utilizing t test to compare dDT and dCT. The number of distortion traces with underlying lesions on optical coherence tomography was also analyzed. RESULTS: Mean age of the subjects was 76.6 (±9.5) years. Each patient traced six reference lines and each was considered a separate case. Out of 30 cases, 17 (56.6%) elicited distortion. Mean percent improvement in distortion was 71.3 ± 23% (p < 0.05). Twelve cases (70.6%) had an underlying lesion (eight cases: disrupted photoreceptor layer and four cases: normal photoreceptor layer). Mean percent improvement in cases with normal photoreceptor layer (90.8 ± 5.45%) was higher than with abnormal photoreceptor layer (58.5 ± 7.17%) (p < 0.05). Five cases with distortion had no associated underlying lesion. Mean percent improvement in these subjects was significantly higher than those with photoreceptor layer disruption. CONCLUSION: Software-generated corrections can potentially correct for perceived distortions in patients with age-related macular degeneration, especially in cases with preserved photoreceptor layer.