An exploratory study to evaluate visual function endpoints in non-advanced age-related macular degeneration.

BACKGROUND: To prevent irreversible vision loss in age-related macular degeneration (AMD), it is critical to detect retinal dysfunction before permanent structural loss occurs. In the current study we evaluated a series of visual function tests to identify potential endpoints to detect visual dysfunction in non-advanced AMD. METHODS: A series of visual function tests were performed on 23 non-advanced AMD subjects (AREDS grade 1-4 on simplified scale) and 34 age-matched normals (AREDS grade 0). Tests included some commonly used endpoints such as ETDRS visual acuity (VA), low luminance (LL) 2.0ND ETDRS VA, MNREAD as well as newly developed tests such as the Ora-VCF™ test, Ora-tablet reading test, color sensitivity etc. Differences between the two groups were compared for each test. Test-retest repeatability and reproducibility was assessed on a subset of subjects and percent agreement was calculated. RESULTS: There was no difference in standard ETDRS VA between non-advanced AMD (0.06 ± 0.02 logMAR) and normal groups (0.04 ± 0.02 logMAR) (p = 0.57). LL 2.0 ETDRS VA and MNREAD showed no difference between the groups (p > 0.05). Ora-VCF™ test was significantly worse in the non-advanced AMD group compared to normals (0.67 ± 0.07 in AMD; 0.45 ± 0.04 in normals, p = 0.005). Non-advanced AMD subjects also had significantly worse reading performance using the Ora-tablet with LL 2.0ND (114.55 ± 11.22 wpm in AMD; 145.17 ± 9.55 wpm in normals p = 0.049). No significant difference between the groups was noted using other tests. Repeatability was 82% for Ora-VCF™ test and 92% for Ora-tablet LL 2.0ND reading. Reproducibility was 89% for both Ora-VCF™ test and Ora-tablet LL 2.0ND reading. CONCLUSION: While there was no significant difference between non-advanced AMD and normal groups using some current common endpoints such as ETDRS VA, LL 2.0 ETDRS VA or MNREAD, Ora-VCF™ test and Ora-tablet LL 2.0ND reading tests were able to identify significant visual dysfunction in non-advanced AMD subjects. These tests show promise as endpoints for AMD studies.

Early Ophthalmic Changes in Macula Does Not Correlate with Visual Function.

PURPOSE: Early detection and treatment of age-related macular degeneration require a clear understanding of the early progress of the disease. The purpose of this study was to investigate whether minimal macular ophthalmoscopic changes corresponded to changes in visual function. METHODS: Color macular photos from a group of older subjects who were classified as grade 0 on AREDS simplified grading were further evaluated by a retinal specialist using 5x magnification for possible minimal macular anomalies. Group 0-A (N = 15) were defined as subjects with no visible macular anomalies while Group 0-B (N = 19) comprised subjects for whom minimal macular mottling, pigment changes or very small drusen (< 63 µm) were observed in the study eye. All subjects had best VA of 20/25 or better and had no evidence of other retinal diseases in the study eye. All subjects underwent a series of visual function tests such as standard ETDRS VA, low luminance ETDRS VA, Pelli-Robson contrast sensitivity, variable contrast flicker (VCF) sensitivity, and reading speed (words per minute, wpm) using both MNRead and low luminance reading on a tablet. RESULTS: There was no significant difference between the mean age between the two groups (74.8 ± 5.2 years for 0-A vs 74.5 ± 4.4 for 0-B, p = 0.82). None of the visual function tests identified any significant difference between the two groups. Mean ETDRS VA was 0.0 ± 0.11 for 0-A subjects and 0.08 ± 0.12 for 0-B (p = 0.063). Mean Pelli-Robson log contrast sensitivity was 1.75 ± 0.29 for 0-A and 1.78 ± 0.17 for the 0-B group (p = 0.73). VCF threshold was 0.47 ± 0.25 for 0-A and 0.43 ± 0.22 for 0-B (p = 0.64). Reading speed using MNRead was 214 ± 47.4 wpm for 0-A and 210 ± 64.7 for 0-B (p = 0.85). Low luminance tablet reading speed was 137 ± 71.8 wpm for 0-A and 151 ± 39.4 (0-B) (p = 0.49). CONCLUSION: A panel of psychophysical tests did not demonstrate significant differences between subjects with and without minimal macular changes.

Postoperative Complications of Pars Plana Vitrectomy for Diabetic Retinal Disease.

Despite recent advances in the medical management of diabetic retinal disease, there remain established indications for vitreoretinal surgery in the treatment of severe proliferative diabetic retinopathy. These include non-clearing vitreous hemorrhage and tractional retinal detachment. Advances in surgical instrumentation, technique, and experience have led to improved visual outcomes, as well as a corresponding decrease in the incidence of postoperative complications. However, the presence of systemic and ocular factors in diabetic patients increases the risk of adverse events compared to non-diabetic individuals. This review will focus on the most important postoperative complications following pars plana vitrectomy, with specific considerations for the diabetic patient.

Visual outcomes from pars plana vitrectomy versus combined pars plana vitrectomy, phacoemulsification, and intraocular lens implantation in patients with diabetes.

PURPOSE: To compare visual acuity outcomes and diabetic retinopathy progression after pars plana vitrectomy (PPV) versus combined pars plana vitrectomy and phacoemulsification (PPVCE) in patients with diabetes. METHODS: Retrospective review of 222 consecutive diabetic patients undergoing PPV or PPVCE. RESULTS: A total of 251 eyes of 222 patients were evaluated (PPV = 122, PPVCE = 129). Four-year follow-up was 64% (161 eyes). Overall, patients undergoing PPVCE had better preoperative visual acuity (PPVCE = 20/80, PPV = 20/160, P = 0.03). At 4-year follow-up, visual acuity improved (PPV = +22, PPVCE = +11 letters) compared with baseline in both groups. After correcting for baseline differences in visual acuity, no statistically significant difference in final visual acuity was observed (PPVCE = 20/32, PPV = 20/50, P = 0.09). Results did not differ substantially by surgical indication (vitreous hemorrhage, traction retinal detachment, epiretinal membrane, and/or diabetic macular edema). Cataract progression occurred in 64%, and cataract surgery was performed in 39% of phakic eyes undergoing PPV. Rates of diabetic retinopathy progression, vitreous hemorrhage, and retinal detachment were not statistically different. Neovascular glaucoma developed in 2 patients (2%) after PPV and 6 patients (8%) after PPVCE (P = 0.07). CONCLUSION: In diabetic patients, equivalent visual acuity improvement over 4 years was observed after PPV or PPVCE. Visual outcomes and retinopathy progression rates were not significantly different after either intervention, suggesting that PPVCE may be appropriate when indicated in patients with diabetes.

Factors associated with visual acuity outcomes after vitrectomy for diabetic macular edema: diabetic retinopathy clinical research network.

PURPOSE: To evaluate factors ¶associated with favorable outcomes after vitrectomy for diabetic macular edema. METHODS: Data were collected prospectively on 241 eyes undergoing vitrectomy for diabetic macular edema. Multivariate models were used to evaluate associations of 20 preoperative and intraoperative factors with 6-month outcomes of visual acuity and retinal thickness. RESULTS: Median central subfield thickness decreased from 412 µm to 278 µm at 6 months, but median visual acuity remained unchanged (20/80, Snellen equivalent). Greater visual acuity improvement occurred in eyes with worse baseline acuity (P < 0.001) and in eyes in which an epiretinal membrane was removed (P = 0.006). Greater reduction in central subfield thickness occurred with worse baseline visual acuity (P < 0.001), greater preoperative retinal thickness (P = 0.001), removal of internal limiting membrane (P = 0.003), and optical coherence tomography evidence of vitreoretinal abnormalities (P = 0.006). No associations with clinician's preoperative assessments of the posterior vitreous were identified. CONCLUSION: These results suggest that the removal of epiretinal membranes may favorably affect visual outcome after vitrectomy. Preoperative presence of vitreoretinal abnormalities appeared to be associated with somewhat greater reductions in retinal thickness but not with visual acuity outcome. These results may be useful for future studies evaluating vitrectomy for diabetic macular edema.

Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral vascular permeability through prekallikrein activation.

Excessive retinal vascular permeability contributes to the pathogenesis of proliferative diabetic retinopathy and diabetic macular edema, leading causes of vision loss in working-age adults. Using mass spectroscopy-based proteomics, we detected 117 proteins in human vitreous and elevated levels of extracellular carbonic anhydrase-I (CA-I) in vitreous from individuals with diabetic retinopathy, suggesting that retinal hemorrhage and erythrocyte lysis contribute to the diabetic vitreous proteome. Intravitreous injection of CA-I in rats increased retinal vessel leakage and caused intraretinal edema. CA-I-induced alkalinization of vitreous increased kallikrein activity and its generation of factor XIIa, revealing a new pathway for contact system activation. CA-I-induced retinal edema was decreased by complement 1 inhibitor, neutralizing antibody to prekallikrein and bradykinin receptor antagonism. Subdural infusion of CA-I in rats induced cerebral vascular permeability, suggesting that extracellular CA-I could have broad relevance to neurovascular edema. Inhibition of extracellular CA-I and kallikrein-mediated innate inflammation could provide new therapeutic opportunities for the treatment of hemorrhage-induced retinal and cerebral edema.

Acute unilateral leukemic hypopyon in an adult with relapsing acute lymphoblastic leukemia.

PURPOSE: To report acute unilateral hypopyon uveitis as an initial presenting feature of relapsing acute lymphoblastic leukemia (ALL) in an adult patient. DESIGN: Observational case report. METHODS: Anterior chamber paracentesis was performed in a 56-year-old male presenting with treatment-resistant unilateral hypopyon while in the remission phase of ALL. RESULTS: Examination of the aqueous humor aspirate revealed presence of malignant cells compatible with the previous bone marrow biopsy and subsequent spinal tap results. CONCLUSIONS: Atypical hypopyon uveitis can be an indication of relapsing ALL, even in adults. Prompt anterior chamber aspiration is required for the correct diagnosis and subsequent treatment.