Salomon Y. Cohen

Prevalence of reticular pseudodrusen in age‐related macular degeneration with newly diagnosed choroidal neovascularisation

Aim: To investigate the prevalence of reticular pseudodrusen (RPD) in eyes of patients presenting with newly diagnosed choroidal neovascularisation (CNV) in age-related macular degeneration (AMD), and to analyse the association between RPD, age-related maculopathy (ARM) and AMD. Method: Two observational consecutive prospective series. In series 1, patients with AMD with newly diagnosed CNV were sampled to determine the incidence of RPD. Eyes with and without RPD were compared by the Mann–Whitney non-parametric test and Fisher’s exact test for age, sex of patients, the eye involved and type of CNV. Series 2 comprised 100 patients referred for fundus photography, fluorescein and/or indocyanine green angiography, for whom pictures showed RPD. This second cohort was then selected from a larger group of patients. Results: Patients with newly diagnosed CNV in series 1 comprised 67 women and 33 men, aged 57–96 years (mean 79.5). CNV was “classic” (32 eyes), “occult” (41) or exhibited vascularised pigment epithelial detachment (PED, 11), retinal angiomatous proliferation (RAP) with or without PED (13), or haemorrhagic or fibrovascular scarring (3). In all, 24 (24%) eyes had RPD. The prevalence of RAP was significantly higher in eyes with RPD than in those without (p = 0.0128), despite the small number of patients with RAP. In series 2, 100 patients with RPD were enrolled in 3 months, and corresponded to 8% of the overall cases referred to our centre (Centre Ophtalmologique d’Imagerie et de Laser, Paris, France). There were 77 women and 23 men, aged 54–93 years (mean 79.2). Eyes with RPD (n = 155) usually exhibited signs of ARM or AMD, including soft drusen (101 eyes) and/or retinal pigment epithelium abnormalities (70), geographical atrophy (27) and/or CNV (61). In both studies, examination of blue-light fundus pictures was extremely helpful in diagnosing RPD. Conclusion: RPD have a high prevalence among patients with AMD with newly diagnosed CNV (24% of cases). RPD were commonly associated with ARM or AMD. This study suggests that eyes with RPD could be classified as a phenotype of ARM.

Results of one-year's treatment with ranibizumab for exudative age-related macular degeneration in a clinical setting.

PURPOSE To evaluate the results of 1 year of treatment with intravitreal ranibizumab for exudative age-related macular degeneration (AMD) in a clinical setting. DESIGN Nonrandomized, single-center, retrospective, interventional case series. METHODS Retrospective analysis of consecutive charts and angiograms of patients with previously untreated exudative AMD, treated in one or both eyes with ranibizumab between January 2 and October 31, 2007. The following were recorded for each patient: age at presentation, gender, treated eye, type of choroidal neovascularization, visual acuity (VA) measured on an Early Treatment Diabetic Retinopathy Study chart at baseline and at 52 +/- 6 weeks, the number of performed intravitreal (IVT) injections, and follow-up examinations. RESULTS The 122 patients comprised 85 women (70%) and 37 men ranging in age from 56 to 91 years (mean +/- standard deviation, 78.3 +/- 7). In all, 124 eyes were treated on a pro re nata basis after 1 or 3 initial IVT injections. The mean number of IVT injections was 3.79 +/- 1.39 (range, 1 to 7). The mean number of follow-up visits was 8.07 +/- 1.44 (range, 4 to 12). Mean VA +/- standard deviation changed from 56.15 +/- 14 to 56.89 +/- 17 letters (VA gain, +0.7 letters). CONCLUSIONS The results showed that VA stabilized rather than improved and compared unfavorably with the gains found in randomized clinical trials and the Prospective Optical Coherence Tomography Imaging of Patients with Neovascular AMD Treated with intraOcular Ranibizumab (PrONTO) Study. However in this study, patients were examined less frequently and were treated far less frequently. The present results suggest that a long, regular follow-up is necessary for patients treated with ranibizumab to obtain and preserve significant visual gain, and not only to achieve visual stabilization.

Changes in visual acuity in patients with wet age-related macular degeneration treated with intravitreal ranibizumab in daily clinical practice: the LUMIERE study.

Purpose: The real-life LUMIERE study on patients with wet age-related macular degeneration treated with intravitreal ranibizumab in 2006 to 2009 showed that failure to follow recommendations was associated with lower efficacy than had been observed in the development phase. The TWIN Study reviewed the situation in 2010 to 2011. Methods: Retrospective, descriptive purely observational study of data acquired after 12 months of treatment with intravitreal ranibizumab. Results: In 881 patients (68% women, mean age, 79 years) treated by 21 ophthalmologists, the mean gain in visual acuity was +4.3 ± 15.4 letters (up from 3.2 ± 14.8 in 2006–2009; NS). Significant improvements were documented in the mean interval between diagnosis and treatment initiation (down from 12.6 ± 26.4–7.7 ± 10.9 days; P < 0.001), and in the percentage of patients who received a full course of induction treatment (56.6 vs. 39.6%; P < 0.001). After induction, hardly any patients were monitored every month as recommended, although retreatment was more assiduous (5.6 ± 2.3 vs. 5.1 ± 2.1 injections; P < 0.001). Conclusion: Despite improvements in key parameters, the effectiveness of intravitreal ranibizumab is still compromised by poor compliance with the guidelines, especially the frequency of postinduction monitoring that is now the most important determinant of successful treatment.

Anti-VEGF drugs as the 2009 first-line therapy for choroidal neovascularization in pathologic myopia.

Background: Pathologic myopia is the second cause of choroidal neovascularization, after age-related macular degeneration (AMD), and the first cause in patients younger than 50 years. The current treatment of subfoveal myopic choroidal neovascularization (mCNV) is verteporfin photodynamic therapy, but its long-term effectiveness has been disappointing. Antivascular endothelial growth factor (anti-VEGF) drugs are now widely used not only to treat choroidal neovascularization in AMD but also for choroidal neovascularization in other conditions. This review summarizes the data supplied by published case series studies about anti-VEGF therapy in mCNV. Methods: Analysis of the current literature allowed discussion of the optimal parameters for mCNV treatment by anti-VEGF, including the choice of anti-VEGF drug, its dose, the treatment protocol, and indications for retreatment. Results: To date, the results of intravitreal bevacizumab or ranibizumab for mCNV have been reported in at least 14 studies, but they were all pilot, monocentric, and noncomparative case series. Nevertheless, they provided useful information on >250 patients and showed similar results, with significant improvement of visual acuity and an excellent safety profile. Conclusion: Shifting from one treatment to another is always difficult in the absence of prospective and controlled comparative studies. However, in 2009, intravitreal ranibizumab or bevacizumab may be considered as first-line therapy for sub- and juxtafoveal mCNV for three reasons: the safety of anti-VEGF drugs and intravitreal injection procedures; the disappointing long-term results of other therapies, including verteporfin treatment; and the excellent convergent results of anti-VEGF therapy in all pilot studies.

Type 2 Neovascularization Secondary To Age-related Macular Degeneration Imaged By Optical Coherence Tomography Angiography

Purpose: Optical coherence tomography angiography is a novel and noninvasive technique for imaging retinal microvasculature by detecting changes in reflectivity that is related to blood flow. The purpose of this study was to describe Type 2 neovascularization characteristics in age-related macular degeneration using optical coherence tomography angiography. Methods: Fourteen eyes of 14 consecutive patients with Type 2 neovascularization were prospectively included. All patients underwent a complete ophthalmological examination, including color and infrared fundus photography, fluorescein and indocyanine green angiography, spectral domain optical coherence tomography angiography, and optical coherence tomography angiography. Results: In all cases, Type 2 lesions could be detected by optical coherence tomography angiography, presenting as a hyperflow lesion in the outer retina, with a glomerulus (4/14) or medusa shape (10/14), surrounded by a dark halo. The superficial layer and the deep retina showed no abnormal flow. Surprisingly, the Type 2 lesions could also be observed in the presumed choriocapillaris layer. These glomerulus- or medusa-shaped lesions were connected, in 10/14 eyes, to a thicker main branch, which seemed to continue deep into the choroidal layers. Conclusion: Optical coherence tomography angiography may be a new imaging method for the diagnosis of Type 2 neovascularization in clinical routine. However, the specificity of the features needs to be investigated in further studies.

Endophthalmitis After Intravitreal Injections: Incidence, Presentation, Management, and Visual Outcome

PURPOSE To report the incidence and characteristics of endophthalmitis after intravitreal injections of anti-vascular endothelial growth factor agents or corticosteroids and to describe the clinical and bacteriologic characteristics, management, and outcome of these eyes with acute endophthalmitis in France. DESIGN Retrospective, nationwide multicenter case series. METHODS From January 2, 2008 to June 30, 2013, a total of 316,576 intravitreal injections from 25 French ophthalmic centers were included. For each center, the number of intravitreal injections was determined using billing codes and the injection protocol was recorded. A registry and hospital records were reviewed to identify patients treated for endophthalmitis after injection during the same time period. The main outcome measures were the incidence of clinical endophthalmitis and visual acuity of endophthalmitis cases. RESULTS During the study period, 65 cases of presumed endophthalmitis were found, giving an overall incidence of 0.021% (2.1 in 10,000 injections) (95% confidence interval [CI], 0.016%-0.026%). The median number of days from injection to presentation was 4 [1-26] days. The most common symptom was vision loss. Bacterial identification was achieved in 43.4%. The most frequent pathogens were gram-positive bacteria (91.3%), including coagulase-negative Staphylococcus in 78.3%. Neither the interval between injection and presentation for endophthalmitis nor the clinical signs differentiated culture-positive from culture-negative cases. In multivariate analysis, the use of a disposable conjunctival mould assist device and the use of prophylaxis with an antibiotic or antiseptic were significantly associated with an increased incidence of endophthalmitis (P = .001). The majority of patients had worse visual acuity after 3 months of follow-up when compared with acuity before endophthalmitis. CONCLUSIONS The incidence of presumed endophthalmitis after intravitreal injections of anti-vascular endothelial growth factors or corticosteroids was low and the prognosis poor. Prevention and management remain challenging. It remains to be determined whether the findings of this study are relevant for other countries using different techniques for intravitreal injections.

Optical Coherence Tomography Angiography in Central Serous Chorioretinopathy

Purpose. To analyze optical coherence tomography angiography (OCTA) findings in eyes with central serous chorioretinopathy (CSC) and to compare them with those obtained with multimodal imaging. Methods. A series of consecutive patients diagnosed with CSC, underwent OCTA and multimodal imaging, including spectral domain OCT, fluorescein, and indocyanine green angiography. OCTA images were performed at three main depth intervals: automatically segmented outer retina, manually adjusted outer retina, and automatically segmented choriocapillaris. Results. Thirty-three eyes of 32 consecutive patients were analyzed. OCTA showed 3 main anomalies at the choriocapillaris: the presence of dark areas (19/33 eyes) which were frequently associated with serous retinal detachment, presence of dark spots (7/33 eyes) which were frequently associated with retinal pigment epithelium detachment, and presence of abnormal vessels (12/33 eyes) which were frequently, but not systematically, associated with choroidal neovascularization, as confirmed by multimodal imaging. Conclusions. OCTA revealed dark areas and dark spots, which were commonly observed. An abnormal choroidal pattern was also observed in one-third of cases, even when multimodal imaging did not evidence any choroidal neovascularization. Abnormal choroidal vessels should be interpreted with caution, and we could assume that this pathological choroidal vascular pattern observed in many CSC cases could be distinct from CNV.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF SUBRETINAL FIBROSIS IN AGE-RELATED MACULAR DEGENERATION.

Purpose: To report the imaging features of subretinal fibrosis secondary to exudative age-related macular degeneration (AMD) on optical coherence tomography angiography. Methods: All consecutive patients diagnosed with subretinal fibrosis complicating exudative AMD were imaged by color retinal photographs or multicolor imaging, fluorescein angiography, spectral domain optical coherence tomography, and optical coherence tomography angiography. Eyes with active exudative features observed during the last 6 months were compared with those without any sign of exudation >6 months. Results: Forty-nine eyes of 47 consecutive patients were included. A blood flow inside the fibrotic scar could be detected in 46 of 49 cases (93.8%). Three patterns of vascular networks could be distinguished, that were described as pruned vascular tree (26 of 49 eyes; 53.1%), tangled network (14 of 49; 28.6%), and/or vascular loop (25 of 49; 51.0%). Furthermore, 2 types of hyporeflective structures, large flow void, and/or dark halo were observed in 63% and in 65% of eyes, respectively. The observed patterns did not differ between eyes with active or inactive lesions. Conclusion: Optical coherence tomography angiography of subretinal fibrosis showed almost constantly a perfused, abnormal vascular network and collateral architectural changes in the outer retina and the choriocapillaris layer. These features were associated with both active and inactive fibrotic choroidal neovessels.

Ultrasound assessment of short-term ocular vascular effects of intravitreal injection of bevacizumab (Avastin®) in neovascular age-related macular degeneration

Acta Ophthalmol. 2010: 88: 641–645

Genotypic Influences on Severity of Exudative Age-Related Macular Degeneration

PURPOSE Major genetic risk factors have recently been identified for age-related macular degeneration (AMD), including the ARMS2/LOC387715 and CFH at-risk polymorphisms. The study was conducted to establish correlations between the AMD genotype and both the phenotype and severity of AMD. METHODS In a prospective cohort of 1216 AMD patients, four genotypic homozygous groups were identified (n = 264): double homozygous for wild-type alleles (group 1, n = 49), homozygous for the at-risk allele of ARMS2/LOC387715 only (group 2, n = 57), homozygous for the at-risk allele of CFH only (group 3, n = 106), and double homozygous for both at-risk alleles (group 4, n = 52). The phenotypic classification of exudative AMD was based on fluorescein angiography. RESULTS Mean age at presentation was significantly lower in group 4 than in group 1 (P < 0.014). Patients in group 4 presented more often with bilateral CNV and fibrovascular scars than did patients in group 1 (P < 0.001 and < 0.0031 respectively) and with significantly lower visual acuity (VA) in the first affected eye than did patients in group 1 (P < 0.02). Patients in group 2 presented with worse VA than did patients in group 3 (P < 0.003). Classic CNV was more commonly associated with the at-risk allele of the ARMS2/LOC387715 locus than with the at-risk allele of the CFH gene (P < 0.026). CONCLUSIONS This study demonstrates an association between the at-risk allele of the ARMS2/LOC387715 locus and classic CNV, fibrovascular lesions, and poor VA. Individuals double homozygous for both at-risk alleles had a higher risk of being affected with a severe form of AMD at an earlier age.