Spontaneous retinal pigment epithelial tear in type 2 choroidal neovascularization: Repair mechanisms following anti-VEGF therapy

BACKGROUND: To report the clinical course and the multimodal retinal imaging of a spontaneous retinal pigment epithelial (RPE) tear in a type 2 choroidal neovascularization (CNV) secondary to age-related macular degeneration treated with anti-vascular endothelial growth factor (VEGF) treatment. CASE PRESENTATION: A 74 year-old man presented with visual acuity deterioration in the right eye. Multimodal retinal imaging showed a predominantly classic (type 2) CNV complicated by a spontaneous RPE tear. The patient received six intravitreal injections of anti-VEGF which resulted in improvement of the vision and stabilization of the neovascular lesion on optical coherence tomography (OCT). Longitudinal changes of the RPE-photoreceptors interface, including RPE splitting, are reported on OCT. CONCLUSION: RPE tears may spontaneously occur in type 2 CNV. Anti-VEGF treatment should be aimed at promoting RPE repair and limiting the extent of the scarring. The mechanisms of RPE repair during treatment may be documented with OCT

Spontaneous resolution of acute syphilitic posterior placoid chorioretinitis: reappraisal of the literature and pathogenetic insights

Acute syphilitic posterior placoid chorioretinitis (ASPPC) is a rare clinical manifestation of ocular syphilis. Spontaneous resolution of this condition has been reported in a few cases.The aim of this manuscript is to report an additional case and to discuss the possible pathogenesis of this condition by reviewing the current evidence on this subject.A 45-year-old man presented to us with decreased vision in the right eye secondary to a placoid macular lesion. Fourteen days after presentation, there was a dramatic improvement of the vision, and multimodal retinal imaging showed almost complete spontaneous resolution of the placoid lesion. Syphilis serology turned out positive and a diagnosis of ASPPC was made. The pathogenesis of ASPPC is unclear, and there is contrasting evidence about the role of the cellular immune system. Since this condition may resolve spontaneously before systemic antimicrobial treatment, the presence of a placoid macular lesion should raise a high suspicion of ASPPC in order to make a timely diagnosis and to avoid progression of untreated syphilis

An interinstitutional comparative study and validation of computer aided drusen quantification

Aims: To assess the portability and clinical applicability of a software program based on Photoshop (Adobe Systems Inc, San Jose, CA, USA) for digital drusen quantification. Methods: Independent graders from the Digital Fundus Photo Reading Center of Columbia University and King’s College Hospital used macular background levelling software to quantify the percentage of drusen in the central and middle Wisconsin subfields. 100 images of consecutive patients with choroidal neovascularisation in one eye and significant drusen in the other eye were analysed to determine suitability, and 10 were chosen for assessment by this software. Results: Of the 10 images used in the interinstitutional validation, the random effects ANOVA for the central and middle subfields showed a high degree of interobserver agreement. The ICC for interobserver reliability was 0.83 (95% CI: 67 to 95) for the central subfield and 0.84 (95% CI: 69 to 99) for the middle subfield. Overall agreement with the manual grading results was good and the within patient coefficient of variation was about 20% for all the pairwise comparisons between observers and the manual stereo gradings. Of the 100 images used to assess practical applicability of the software, 79 were suitable for semiautomated analysis. 13 had extensive mixed retinal pigment epithelial (RPE) changes limiting drusen identification, five had a significant number of reticular drusen, which are poorly identified by the software, and three had multiple small areas of RPE atrophy, which are difficult to distinguish from drusen. Conclusions: The software was successfully used by two institutions demonstrating portability, with good correlation between graders and to the manual stereo grading. Digital drusen quantification was possible in 79% of the images analysed

Autofluorescence characteristics of early, atrophic, and high-risk fellow eyes in age-related macular degeneration.

PURPOSE: To assess the relationships of drusen, pigment, and focally increased autofluorescence (FIAF) and the reticular pattern of hypoautofluorescence, to distinguish the combined photographic and AF characteristics of early, atrophic, and high-risk fellow eyes in AMD. METHODS: In a retrospective interinstitutional clinical study, AF and color photograph pairs of 221 eyes were examined: 166 eyes of 83 patients with bilateral large, soft drusen, with and without geographic atrophy (GA), and 55 fellow eyes of 55 patients with unilateral choroidal neovascularization (CNV). Forty-two eyes (one eye from each of 42 patients with early or atrophic AMD) were divided into four groups: 14 with drusen only, 9 with drusen and pigment abnormalities, 11 fellow eyes of patients with unilateral GA, and 8 eyes of patients with bilateral GA (acronyms for the groups: D-D, D-Pig, D-GA and GA-GA, respectively). The 55 fellow eyes of patients with CNV were divided into three groups: 19 eyes with no FIAF (CNV-0), 16 with FIAF without reticular AF (CNV-1), and 20 eyes with reticular AF and/or pseudodrusen (CNV-R). Image pairs of eyes with FIAF were registered, and drusen, pigment, and FIAF were segmented using automated background leveling and thresholding. All 221 eyes were surveyed for reticular AF and reticular pseudodrusen. The main outcome measures were (1) the fraction and relative probability of FIAF colocalizing with drusen and pigment and (2) the presence or absence of reticular AF and reticular pseudodrusen. RESULTS: The mean fractions of FIAF that colocalized with large drusen were: D-D group, 0.46 +/- 0.21; D-Pig group, 0.42 +/- 0.29; D-GA group, 0.13 +/- 0.09; and GA-GA group, 0.11 +/- 0.12. Comparisons between groups showed significant differences when comparing either the D-D group or the D-Pig group with either the D-GA group or the GA-GA group (P between 0.0001 and 0.015), whereas other comparisons were nonsignificant (Mann-Whitney rank sum test). The mean probabilities of FIAF colocalizing with large drusen relative to chance (1.0) were: D-D group, 4.7 +/- 2.5; D-Pig group, 4.3 +/- 2.3; D-GA group, 1.4 +/- 0.8; and GA-GA group, 1.8 +/- 1.3, with similar significant differences as for the colocalization fractions. The mean probability of FIAF colocalizing with small to intermediate drusen in the D-D group was 1.5 +/- 1.3, which was not significantly different from chance. In the D-Pig group, the median probability of FIAF colocalizing with pigment abnormalities was 10.0 (range, 1.1-51.0). The AF patterns in 15 of 19 eyes in the CNV-0 group were normal; the remainder had nonreticular hypoautofluorescence only. In the CNV-1 group, the relations of FIAF with drusen and pigment were similar to those in the early AMD groups. CNV-R comprised 20 of 55 eyes in the CNV group, but reticular autofluorescence and/or pseudodrusen were found in only 14 of 166 eyes of the early and atrophic groups. Of the 34 total eyes with reticular AF or pseudodrusen, 28 had both, 4 had reticular AF only, and 2 had reticular pseudodrusen only. CONCLUSIONS: There are clear relationships between AF patterns and clinical AMD status. In early AMD, FIAF's colocalization with large, soft drusen and hyperpigmentation is several times greater than chance, suggesting linked disease processes. In advanced atrophic AMD, FIAF is found mostly adjacent to drusen and GA, suggesting that dispersal of drusen-associated lipofuscin is a marker of atrophic disease progression. In the neovascular case, a large group of fellow eyes have no FIAF abnormalities, suggesting that lipofuscin is not a major determinant of CNV. However, reticular hypoautofluorescence, consistent with widespread inflammatory damage to the RPE, appears to be a highly sensitive imaging marker for the disease that determines reticular pseudodrusen and is strongly associated with CNV

Current advances in the treatment of neovascular age-related macular degeneration

Introduction: Age-related macular degeneration (AMD) is the most common cause of permanent central visual acuity loss in persons over 65 years of age in industrialized nations. Today, intravitreal vascular endothelial growth factor (VEGF) inhibitors are the mainstay of treatment worldwide. Areas covered: The following review covers the current treatments and challenges of wet AMD management. It also covers emerging therapies including radiation, latest generation anti-VEGF agents, and combination therapies. Expert opinion: Current neovascular AMD therapy is aimed at decreasing the VEGF effect at the choroidal neovascularization (CNV) complex. The most important existing challenges in the treatment of neovascular AMD are improving visual outcomes, decreasing the treatment burden, and minimizing geographic atrophy. Clinicians are using many treatment strategies to minimize intravitreal injections without sacrificing visual outcomes. Combination of anti-VEGF therapy with other previously available treatments that target a different pathophysiological mechanism may be a reasonable clinical strategy to minimize intravitreal injections. Many exciting novel drugs that target newly discovered pathways associated with CNV development and progression hold clinical promise. The results of ongoing randomized clinical trials will answer the important concerns surrounding new drugs and delivery devices: safety and visual outcomes

Drusen classification in bilateral drusen and fellow eye of exudative age-related macular degeneration.

AIM: To assess the value of the modified international classification system in screening high-risk patients with bilateral age-related maculopathy (ARM) from those with lower risk characteristics. METHODS: In total, 164 digital images of 106 patients with either bilateral ARM (group A) or the fellow eyes of unilateral exudative age-related macular degeneration (AMD) (Group B) were included. Patients with no signs of ARM in both eyes or those with bilateral late AMD were excluded. The images were randomised and then graded by two masked ophthalmologists based on the modified International Classification of ARM. RESULTS: The interobserver consistency between the two graders was high with a Kappa value of 0.82 (SE 0.34, P<0.0001). There were no significant differences in the distribution of the stages of ARM between the two subgroups. Stage 3 was the most common stage in each group for both graders followed by stage 2a in the bilateral drusen group. Stages 1a, 2a and 2b were equally the next common stage in the fellow eye of chordial neovascularisation group. CONCLUSION: A screening system based on clinical characteristics would be of value in risk prediction in a clinical setting. Type of Drusen alone, as identified by the modified International grading system, may not be reliably predictive in screening for patients who are at high risk of developing choroidal neovascularisation