Chiara M. Eandi

Photodynamic Therapy for Chronic Central Serous Chorioretinopathy

Purpose To determine whether photodynamic therapy (PDT) is effective for treatment of chronic central serous chorioretinopathy (CSC). Methods Sixteen eyes with chronic CSC and macular detachment documented by optical coherence tomography (OCT) received PDT guided by indocyanine green (ICG) angiography according to the parameters outlined in the TAP Study. One or more laser spots were applied to the areas of choroidal vascular hyperpermeability that corresponded to retinal pigment epithelium decompensation. Patients were observed for 6 to 12 months. Two PDT sessions 1 month apart were performed on 2 eyes. Examinations included visual acuity measurement, fundus biomicroscopy, fluorescein and ICG angiography, and OCT. Results Macular exudation resolved completely in 13 eyes (81%) and partially regressed in 3. Choriocapillaris hypoperfusion was shown by ICG angiography for several months at the site of PDT application. Visual acuity improved 1 to 4 lines in 11 eyes and was unchanged in 5 eyes. Conclusions ICG-guided PDT performed according to the parameters outlined by the TAP Study seems effective for treating chronic CSC. Further studies are needed to verify treatment safety and the time and rate of recurrences.

Optical coherence tomography in unilateral resolved central serous chorioretinopathy.

Purpose: To evaluate the correlation between optical coherence tomographic evaluations of foveal thickness and anatomical changes within the fovea and visual acuity in patients who have unilateral resolved central serous chorioretinopathy. Methods: A retrospective review of cases of unilateral resolved central serous chorioretinopathy imaged with high-resolution optical coherence tomography was performed. The foveal thickness of the involved eye was normalized by dividing its thickness by that of the uninvolved fellow eye. The best-corrected visual acuity of the involved eye was normalized as well. The normalized foveal thickness was compared with the normalized visual acuity. The anatomical findings of the fovea were compared with the visual acuity. Results: Twenty patients were evaluated (11 men and 9 women; age range, 31–66 years [mean, 46.8 years]). The mean foveal thickness was 135.8 &mgr;m in the involved eyes and 184.4 &mgr;m in the uninvolved eyes (P < 0.001). There was a correlation between the normalized foveal thickness and the normalized visual acuity (Spearman &rgr;, 0.67; P = 0.001). The external limiting membrane was visible in 7 (35%) of the involved eyes compared with 19 uninvolved eyes (95%) (P < 0.001). In the involved eyes, those with a visible external limiting membrane had better visual acuity than did those that did not (P = 0.001). It was possible to visualize the boundary between the photoreceptor cell bodies and the outer segments in 8 (40%) of the involved eyes and in the 17 uninvolved eyes (85%) (P < 0.001). In the involved eyes, those with a visible boundary between the photoreceptor bodies and the outer segments had a better visual acuity than did those that did not (P = 0.019). Conclusions: Patients with unilateral resolved central serous chorioretinopathy had a decrease in the central foveal thickness in the involved eyes, and there was a statistically significant correlation between the foveal thickness and the visual acuity, even in eyes with relatively good visual acuity. The inability to observe a discrete signal corresponding to the external limiting membrane layer was more common in involved eyes and was significantly associated with decreased visual acuity. This same relationship was seen with the ability to visualize the boundary between the photoreceptor bodies and the outer segments; this boundary was less commonly observed in involved eyes and was associated with decreased visual acuity. Resolved central serous chorioretinopathy causes a number of morphologic changes in the fovea that are associated with visual acuity.

Acute central serous chorioretinopathy and fundus autofluorescence

Objectives: To describe fundus autofluorescence (FAF) in a series of patients with acute central serous chorioretinopathy (CSC). Methods: Nine eyes of six patients with acute CSC were evaluated with fluorescein angiography (FA) and FAF imaging to evaluate the nature of the focal retinal pigment epithelial (RPE) leak evident with FA. Results: All nine eyes in this series demonstrated hypoautofluorescence corresponding precisely to the site of the focal RPE leak seen on FA. Conclusions: In this group of patients, the acute focal RPE leaks seen with FA corresponded precisely to an area of hypoautofluorescence imaged with FAF. This observation supports the concept that a mechanical defect or absence of the RPE accounts for the leakage from the inner choroid to the subneurosensory space in CSC. FAF is also a useful noninvasive diagnostic adjunct to identify the focal RPE leak in patients with acute CSC.

Selective photodynamic therapy for neovascular age-related macular degeneration with polypoidal choroidal neovascularization.

Purpose: To evaluate the efficacy of selective treatment with indocyanine green (ICG) angiography-guided photodynamic therapy (PDT) with verteporfin for polypoidal choroidal vasculopathy (PCV). Methods: In this retrospective consecutive series, 30 eyes of 30 patients with PCV were included. Complete ocular examination, digital fluorescein angiography (FA), ICG angiography, and optical coherence tomography were performed at baseline and at standard intervals thereafter. ICG angiography-guided PDT was performed on all eyes. Only the area of the active PCV or “hot spot” evident on the ICG angiogram was treated. A spot size was chosen to cover the active neovascular lesion with a 200-&mgr;m border. Retreatment was performed when angiography revealed a recurrent lesion. Results: Thirty eyes with PCV were treated and followed for 1 year. Mean age of the patients was 75 years (range, 55–90 years). These patients were all classified as having occult choroidal neovascularization (CNV) with FA and polypoidal CNV with ICG angiography. Improvement of vision (≥3 lines) was achieved in 15 eyes (50%). Nine eyes had stable vision (30%), and 6 eyes (20%) had a decrease in vision (≥3 lines). Repeated treatment was required in 15 eyes (50%) for an average of 2.2 treatments in 1 year. Conclusion: This study indicates that stabilization or improvement of vision is achieved in most eyes (80%) with neovascular AMD from PCV after selected ICG angiography-guided PDT. These outcomes compare very favorably with those in previous reports on the treatment of occult CNV. Reduced collateral damage to the choriocapillaris and reduced upregulation of vascular endothelial growth factor are presumed to be the explanation for this apparently better outcome. Further studies with longer follow-up are warranted to investigate the long-term efficacy in these conditions.

Acute syphilitic posterior placoid chorioretinitis: report of a case series and comprehensive review of the literature.

Purpose: To describe the clinical and angiographic features of a series of patients with acute syphilitic posterior placoid chorioretinitis (ASPPC) in the context of previously published cases. Methods: A retrospective, noncomparative, multicenter chart review was performed on 16 patients with active ASPPC. Positive serologic tests supported the diagnosis in all patients. Color and red-free photographs as well as fluorescein angiography were obtained in each case. Indocyanine green angiography, optical coherence tomography, and fundus autofluorescence were performed on selected patients. A total of 44 previously published cases of ASPPC were identified using both a Medline Search and references listed in articles identified. Results: Ocular involvement was bilateral in 9 of our 16 patients (56.3%). The mean and median ages at presentation were 40 and 38 years, respectively (range 28–57 years). Nine patients (56.3%) were human immunodeficiency virus positive, with most recent CD4 cell counts ranging from 160 cells/&mgr;L to 450 cells/&mgr;L and a median CD4 cell count of 250 cells/&mgr;L. Seven of 16 patients (43.8%) had a history of mucocutaneous manifestations of secondary syphilis, whereas 4 (25.0%) had evidence of neurosyphilis. Anterior chamber and/or vitreous inflammation was evident in 13 patients (81.3%). Fifteen of 16 patients had positive venereal disease research laboratory or rapid plasma regain titers, and 13 of 13 tested patients had a positive serum fluorescent treponemal antibody absorption. The initial vision in the 25 affected eyes ranged from 20/20 to counting fingers, with a median of 20/80. In all patients, posterior segment examination in the involved eyes revealed a large, yellowish, placoid, outer retinal lesion. Fluorescein angiography showed progressive hyperfluorescence in the area of the lesion, often with scattered focal hypofluorescence, or leopard spotting. Inflammation subsided, the yellowish lesions resolved, and vision improved shortly after antibiotic therapy in 20 of 25 affected eyes. Visual acuity at last visit ranged from 20/20 to 20/150, with a median final vision of 20/25. A review of the literature revealed 44 previously reported cases of ASPPC. Shared demographic, clinical, and angiographic features were summarized. Conclusion: Acute syphilitic posterior placoid chorioretinitis is an uncommon but clinically and angiographically distinct manifestation of ocular syphilis. All patients with characteristic clinical and angiographic findings of ASPPC should be tested for both neurosyphilis and human immunodeficiency virus coinfection. Vision recovery typically followed completion of appropriate antibiotic therapy.

Artifacts in automatic retinal segmentation using different optical coherence tomography instruments.

Purpose: The purpose of this study was to compare and evaluate artifact errors in automatic inner and outer retinal boundary detection produced by different time-domain and spectral-domain optical coherence tomography (OCT) instruments. Methods: Normal and pathologic eyes were imaged by six different OCT devices. For each instrument, standard analysis protocols were used for macular thickness evaluation. Error frequencies, defined as the percentage of examinations affected by at least one error in retinal segmentation (EF-exam) and the percentage of total errors per total B-scans, were assessed for each instrument. In addition, inner versus outer retinal boundary delimitation and central (1,000 &mgr;m) versus noncentral location of errors were studied. Results: The study population of the EF-exam for all instruments was 25.8%. The EF-exam of normal eyes was 6.9%, whereas in all pathologic eyes, it was 32.7% (P < 0.0001). The EF-exam was highest in eyes with macular holes, 83.3%, followed by epiretinal membrane with cystoid macular edema, 66.6%, and neovascular age-related macular degeneration, 50.3%. The different OCT instruments produced different EF-exam values (P < 0.0001). The Zeiss Stratus produced the highest percentage of total errors per total B-scans compared with the other OCT systems, and this was statistically significant for all devices (P ≤ 0.005) except the Optovue RTvue-100 (P = 0.165). Conclusion: Spectral-domain OCT instruments reduce, but do not eliminate, errors in retinal segmentation. Moreover, accurate segmentation is lower in pathologic eyes compared with normal eyes for all instruments. The important differences in EF among the instruments studied are probably attributable to analysis algorithms used to set retinal inner and outer boundaries. Manual adjustments of retinal segmentations could reduce errors, but it will be important to evaluate interoperator variability.

Haplotypes in IL-8 Gene Are Associated to Age-Related Macular Degeneration: A Case-Control Study

Background Age-related macular degeneration (AMD) is the main cause of blindness in the developed world. The etiology of AMD is multifactorial due to the interaction between genetic and environmental factors. IL-8 has a role in inflammation and angiogenesis; we report the genetic characterization of IL-8 allele architecture and evaluate the role of SNPs or haplotypes in the susceptibility to wet AMD, case-control study. Methods Case-control study including 721 AMD patients and 660 controls becoming from Italian population. Genotyping was carried out by Real Time-PCR. Differences in the frequencies were estimated by the chi-square test. Direct sequencing was carried out by capillary electrophoresis trough ABI3130xl. Results rs2227306 showed a p–value of 4.15*10−5 and an Odds Ratio (OR) for T allele of 1.39 [1.19–1.62]. After these positive results, we sequenced the entire IL-8 regulatory and coding regions of 60 patients and 30 controls stratified for their genotype at rs2227306. We defined two different haplotypes involving rs4073 (A/T), rs2227306 (C/T), rs2227346 (C/T) and rs1126647 (A/T): A-T-T-T (p-value: 2.08*10−9; OR: 1.68 [1.43–1.97]) and T-C-C-A (p-value: 7.07*10−11; OR: 0.60 [0.51–0.70]). To further investigate a potential functional role of associated haplotypes, we performed an expression study on RNA extracted from whole blood of 75 donors to verify a possible direct correlation between haplotype and gene expression, failing to reveal significant differences. Conclusions These results suggest a possible secondary role of IL-8 gene in the development of the disease. This paper outlines the importance of association between inflammation and AMD. Moreover IL-8 is a new susceptibility genomic biomarker of AMD.

Anecortave acetate treatment for retinal angiomatous proliferation: a pilot study.

Purpose: The purpose of this study was to evaluate anecortave acetate treatment of retinal angiomatous proliferation (RAP), a neovascular form of age-related macular degeneration, with specific regard to inhibition of neovascularization and maintenance of vision. Methods: Thirty-four patients with RAP with any stage of neovascularization were randomized 1:1:1 for treatment with three different quantities (30 mg, 15 mg, 3 mg) of anecortave acetate sterile suspension for juxtascleral administration. Best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study chart), intraocular pressure measurement, biomicroscopy, funduscopy, digital fluorescein, and indocyanine green angiography were recorded at baseline and at 3 months. A 6-month retreatment interval was established for this study with a follow-up of 12 months. In selected patients optical coherence tomography was performed. The outcomes were mean changes in visual acuity and lesion size at 1 year. Results: The detachment of the neurosensory retina and retinal pigment epithelium improved in all eyes, but all neovascular lesions increased in size. Vision loss occurred in the majority of study eyes (22 out of 34 eyes, 64.7%) independent of the concentration administered. Conclusion: The results suggest that a posterior juxtascleral injection of anecortave acetate reduces capillary permeability in patients with RAP. However, in spite of improvement of the exudation there is a progression of neovascularization and a significant loss of vision in all these patients. Like other monotherapeutic methods used to treat this variant of neovascular age-related macular degeneration, anecortave acetate alone does not appear to benefit these patients. Future studies should investigate a combination form of therapy.

Aflibercept, bevacizumab and ranibizumab prevent glucose-induced damage in human retinal pericytes in vitro, through a PLA2/COX-2/VEGF-A pathway.

Diabetic retinopathy, a major cause of vision loss, is currently treated with anti-VEGF agents. Here we tested two hypotheses: (i) high glucose damages retinal pericytes, the cell layer surrounding endothelial cells, via VEGF induction, which may be counteracted by anti-VEGFs and (ii) activation of PLA2/COX-2 pathway by high glucose might be upstream and/or downstream of VEGF in perycites, as previously observed in endothelial cells. Human retinal pericytes were treated with high glucose (25mM) for 48h and/or anti-VEGFs (40μg/ml aflibercept, 25μg/ml bevacizumab, 10μg/ml ranibizumab). All anti-VEGFs significantly prevented high glucose-induced cell damage (assessed by LDH release) and improved cell viability (assessed by MTT and Evans blue). High glucose-induced VEGF-A expression, as detected both at mRNA (qPCR) and protein (ELISA) level, while receptor (VEGFR1 and VEGFR2) expression, detected in control condition, was unaffected by treatments. High glucose induced also activation of PLA2/COX-2 pathway, as revealed by increased phosphorylation of cPLA2, COX-2 expression and PGE2 release. Treatment with cPLA2 (50μM AACOCF3) and COX-2 (5μM NS-392) inhibitors prevented both cell damage and VEGF-A induced by high glucose. Finally, challenge with exogenous VEGF-A (10ng/ml) induced VEGF-A expression, while anti-VEGFs reduced VEGF-A expression induced by either high glucose or exogenous VEGF-A. These data indicate that high glucose directly damages pericytes through activation of PLA2/COX-2/VEGF-A pathway. Furthermore, a kind of feed-forward loop between cPLA2/COX-2/PG axis and VEGF appears to operate in this system. Thus, anti-VEGFs afford protection of pericytes from high glucose by inhibiting this loop.

Anecortave Acetate For The Treatment Of Idiopathic Perifoveal Telangiectasia: A Pilot Study

Purpose: To investigate the use of anecortave acetate, a new angiostatic cortisene, for the treatment of the leakage and/or neovascularization associated with idiopathic perifoveal telangiectasia (IPT) in an open label prospective pilot study. Methods: Seven eyes of six patients were treated with posterior juxtascleral administration of anecortave acetate delivered adjacent to the macula using a specially designed curved cannula. A full clinical examination and fluorescein angiography were performed at baseline and at 3-month intervals. The primary efficacy outcome for this pilot study was the mean change in visual acuity (Early Treatment Diabetic Retinopathy Study) from baseline. Results: The visual acuity remained unchanged in two eyes of two patients with nonproliferative disease after 24 months. The five eyes of four patients presenting with subretinal neovascularization, the proliferative stage of IPT, showed stabilization or improvement of lesion size, resolution of leakage, and stabilization of vision at last follow-up. Conclusion: The results of this study suggest that anecortave acetate may inhibit retinal and subretinal permeability as well as neovascular proliferation in patients with IPT. A larger study accordingly should be designed in the future to evaluate the effectiveness and treatment of IPT with this drug.