Progression of retinal pigment epithelial atrophy in stargardt disease

• PURPOSE: To evaluate retinal pigment epithelial (RPE) atrophy in patients with Stargardt disease using autofluorescence imaging (AF). • DESIGN: Retrospective observational case series. • METHODS: Demographics, best-corrected visual acuity (BCVA), AF images, and electrophysiology responses (group 1, macular dysfunction; group 2, macula + cone dysfunction; group 3, macula + cone-rod dysfunction) were evaluated at presentation and follow-up in a group of 12 patients (24 eyes) with Stargardt disease. The existence, development, and rate of enlargement of areas of RPE atrophy over time were evaluated using AF imaging. A linear regression model was used to investigate the effects of AF and electrophysiology on rate of atrophy enlargement and BCVA, adjusting for age of onset and duration of disease. • RESULTS: Eight male and 4 female patients (median age 42 years; range 24-69 years) were followed for a median of 41.5 months (range 13-66 months). All 12 patients had reduced AF compatible with RPE atrophy at presentation and in all patients the atrophy enlarged during follow-up. The mean rate of atrophy enlargement for all patients was 1.58 mm /y (SD 1.25 mm /y; range 0.13-5.27 mm /y). Only the pattern of functional loss present as detected by electrophysiology was statistically significantly associated with the rate of atrophy enlargement when correcting for other variables (P <.001), with patients in group 3 (macula + cone-rod dysfunction) having the fastest rate of atrophy enlargement (1.97 mm /y, SD 0.70 mm /y) (group 1 [macula] 1.09 mm /y, SD 0.53 mm /y; group 2 [macula + cone] 1.89 mm /y, SD 2.27 mm /y). • CONCLUSION: Variable rates of atrophy enlargement were observed in patients with Stargardt disease. The pattern of functional loss detected on electrophysiology was strongly associated with the rate of atrophy enlargement over time, thus serving as the best prognostic indicator for patients with this inherited retinal disease. © 2012 Elsevier Inc. All rights reserved.

Classification of fundus autofluorescence patterns in early age-related macular disease

PURPOSE. To describe and classify patterns of abnormal fundus autofluorescence (FAF) in eyes with early nonexudative age-related macular disease (AMD). METHODS. FAF images were recorded in eyes with early AMD by confocal scanning laser ophthalmoscopy (cSLO) with excitation at 488 nm (argon or OPSL laser) and emission above 500 or 521 nm (barrier filter). A standardized protocol for image acquisition and generation of mean images after automated alignment was applied, and routine fundus photographs were obtained. FAF images were classified by two independent observers. The ? statistic was applied to assess intra- and interobserver variability. RESULTS. Alterations in FAF were classified into eight phenotypic patterns including normal, minimal change, focal increased, patchy, linear, lacelike, reticular, and speckled. Areas with abnormal increased or decreased FAF signals may or may not have corresponded to funduscopically visible alterations. For intraobserver variability, ? of observer I was 0.80 (95% confidence interval [CI]0.71-0.89) and of observer II, 0.74. (95% CI, 0.64-0.84). For interobserver variability, ? was 0.77 (95% CI, 0.67-0.87). CONCLUSIONS. Various phenotypic patterns of abnormal FAF can be identified with cSLO imaging. Distinct patterns may reflect heterogeneity at a cellular and molecular level in contrast to a nonspecific aging process. The results indicate that the classification system yields a relatively high degree of intra- and interobserver agreement. It may be applicable for determination of novel prognostic determinants in longitudinal natural history studies, for identification of genetic risk factors, and for monitoring of future therapeutic interventions to slow the progression of early AMD. Copyright © Association for Research in Vision and Ophthalmology.

Heavier-than-water silicone oil mixture as a long-term tamponade agent:A pilot study

Purpose: To evaluate the tamponade effect on the retina of a heavier-than-water silicone oil mixture and to compare it with the effect of silicone oil. Methods: Prospective, non-randomised, comparative pilot study. Phakic/pseudophakic patients with retinal detachment undergoing vitrectomy with Densiron 68 or silicone oil were recruited. The 'separation volume', defined as the relative volume of the space between intraocular tamponade agent and retina, was estimated using magnetic resonance imaging in both groups and compared. Results: Nine participants were included; 4 received silicone oil and 5 Densiron 68. The mean separation volume was statistically significantly larger in the silicone oil group (0.477 ± 0.419 cm ) than in the Densiron group (0.042 ± 0.013 cm ; p = 0.014). Conclusions: In this study Densiron achieved an excellent tamponade effect in the retina. © 2011 S. Karger AG, Basel.

Cost-effectiveness of internal limiting membrane peeling versus no peeling for patients with an idiopathic full-thickness macular hole:Results from a randomised controlled trial

Aim: To determine whether internal limiting membrane (ILM) peeling is cost-effective compared with no peeling for patients with an idiopathic stage 2 or 3 full-thickness macular hole. Methods: A cost-effectiveness analysis was performed alongside a randomised controlled trial. 141 participants were randomly allocated to receive macular-hole surgery, with either ILM peeling or no peeling. Health-service resource use, costs and quality of life were calculated for each participant. The incremental cost per quality-adjusted life year (QALY) gained was calculated at 6 months. Results: At 6 months, the total costs were on average higher (£424, 95% CI -182 to 1045) in the No Peel arm, primarily owing to the higher reoperation rate in the No Peel arm. The mean additional QALYs from ILM peel at 6 months were 0.002 (95% CI 0.01 to 0.013), adjusting for baseline EQ-5D and other minimisation factors. A mean incremental cost per QALY was not computed, as Peeling was on average less costly and slightly more effective. A stochastic analysis suggested that there was more than a 90% probability that Peeling would be cost-effective at a willingness-to-pay threshold of £20 000 per QALY. Conclusion: Although there is no evidence of a statistically significant difference in either costs or QALYs between macular hole surgery with or without ILM peeling, the balance of probabilities is that ILM Peeling is likely to be a cost-effective option for the treatment of macular holes. Further long-term follow-up data are needed to confirm these findings.

A Longitudinal Study of Stargardt Disease: Clinical and Electrophysiologic Assessment, Progression, and Genotype Correlations

Purpose: To investigate the clinical and electrophysiologic natural history of Stargardt disease and correlate with the genotype. Design: Cohort study of 59 patients. Methods: Clinical history, examination, and electrophysiologic assessment were undertaken in a longitudinal survey. Patients were classified into 3 groups based on electrophysiologic findings, as previously published: Group 1 had dysfunction confined to the macula; Group 2 had macular and generalized cone system dysfunction; and Group 3 had macular and both generalized cone and rod system dysfunction. At baseline, there were 27 patients in Group 1, 17 in Group 2, and 15 in Group 3. Amplitude reduction of >50% in the relevant electroretinogram (ERG) component or a peak time shift of >3 ms for the 30 Hz flicker ERG or bright flash a-wave was considered clinically significant ERG deterioration. Molecular screening of ABCA4 was undertaken. Results: The mean age at baseline was 31.7 years, with the mean follow-up interval being 10.5 years. A total of 22% of patients from Group 1 showed ERG group transition during follow-up, with 11% progressing to Group 2 and 11% to Group 3. Forty-seven percent of patients in Group 2 progressed to Group 3. There was clinically significant ERG deterioration in 54% of all subjects: 22% of Group 1, 65% of Group 2, and 100% of Group 3. At least 1 disease-causing ABCA4 variant was identified in 47 patients. Conclusions: All patients with initial rod ERG involvement demonstrated clinically significant electrophysiologic deterioration; only 20% of patients with normal full-field ERGs at baseline showed clinically significant progression. Such data assist counseling by providing more accurate prognostic information and are also highly relevant in the design, patient selection, and monitoring of potential therapeutic interventions. © 2013 Elsevier Inc. All rights reserved.

Internal Limiting Membrane Peeling in Vitreo-retinal Surgery

Peeling the internal limiting membrane of the retina has become a very common procedure performed by vitreo-retinal surgeons. The combination of new microsurgical instrumentation with the availability of different dyes to stain this thin and transparent membrane has facilitated the performance of internal limiting membrane peeling, reducing the time and trauma associated with this maneuver. Internal limiting membrane peeling has been used to treat a variety of retinal pathologies, including full-thickness macular hole, epiretinal membrane, macular edema, vitreomacular traction syndrome, and Terson syndrome, among others. Although it appears that peeling the internal limiting membrane in these retinal conditions may be associated with better anatomical and visual outcomes following surgery, further evidence through randomized controlled clinical trials is still needed to guide the vitreo-retinal surgeon on the appropriate use of this surgical maneuver. © 2008 Elsevier Inc. All rights reserved.

Punctate inner choroidopathy

Punctate inner choroidopathy (PIC) is a relatively uncommon inflammatory multifocal chorioretinopathy that affects predominantly young myopic women. It is characterized by the presence of multiple, small, well-defined, yellow-white fundus lesions frequently limited to the posterior pole in the absence of flare and inflammatory cells in the anterior chamber or vitreous cavity. Most patients with PIC do not require treatment, as the disease does not often threaten vision; however, when subfoveal choroidal neovascular membrane (CNV) ensues, patients usually lose sight rapidly, requiring immediate care. Treatment modalities that have been used to manage patients with PIC and subfoveal CNV include systemic and local steroids, other immunosuppressant agents, laser photocoagulation, photodynamic therapy, submacular surgery and, most recently, anti-vascular endothelial growth factor therapy. To date, however, there is no clear consensus on the effective therapy. Further research into this area, as well as on the cause and possible predisposing factors for PIC, is warranted. © 2011 Elsevier Inc.

Fundus autofluorescence in patients with age-related macular degeneration and high risk of visual loss

PURPOSE: To describe fundus autofluorescence (AF) patterns and their change over time in patients with age-related macular degeneration (AMD) and high risk of visual loss participating in the drusen laser study (DLS). DESIGN: Randomized clinical trial. METHODS: The study population consisted of 29 patients (35 eyes) participating in the DLS, which is a prospective, randomized, controlled clinical trial of prophylactic laser therapy in patients with AMD and high risk of neovascular complications. The intervention consisted of 16 eyes having prophylactic laser and 19 receiving no treatment. The main outcome measures were changes in the distribution of drusen and AF. Patients were reviewed for a median follow-up or 24 months (range 12-36 months). RESULTS: At baseline, four patterns of fundus AF were recognized: focal increased AF (n = 18), reticular AF (n = 3), combined focal and reticular AF (n = 2), and homogeneous AF (n = 12). At last follow-up, fundus AF remained unchanged in 15 untreated (78%) and in seven treated (43%) eyes. In only one untreated eye, focal areas of increased AF returned to background levels and were no longer detectable at last follow-up, compared with six treated eyes. This difference was statistically significant (P = .03). Only large foveal soft drusen (drusenoid pigment epithelium detachments) consistently corresponded with focal changes in AF, whereas no obvious correspondence was found between small soft drusen located elsewhere and changes in AF. CONCLUSION: The lack of obvious correspondence between the distribution of drusen and of AF found in this study appears to indicate that drusen and AF represent independent measures of aging in the posterior pole. © 2002 Elsevier Science Inc. All rights reserved.

Long-term graft survival in patients with flexible open-loop anterior chamber intraocular lenses

Purpose. To evaluate the long-term graft survival in patients with flexible open-loop anterior chamber intraocular lenses (AC IOL). Methods. We retrospectively reviewed the records of patients with aphakic/pseudophakic bullous keratopathy who underwent penetrating keratoplasty and flexible open-loop AC IOL implantation in our institution from 1983 to 1988. Results. 79 eyes from 77 patients were included in the study. Mean follow-up was 50 months (range 1 to 123 months). At last follow-up 61 eyes (77.2%) had clear grafts. Among them, the visual acuity was = 20/40 in 14 eyes (23.0%), 20/50-20/100 in 22 eyes (36.1%), 20/200-20/400 in 9 eyes (14.8%) and = CF in 16 (26.2%). Increment of glaucoma medications and/or glaucoma surgery was the most frequent complication (37 eyes, 46,8%). Cystoid macular edema was newly diagnosed in 10 eyes (12.7%). Conclusions. Flexible, open-loop anterior chamber lens are a viable option in the treatment of patients with aphakic or pseudophakic bullous keratopathy undergoing penetrating keratoplasty.