Lise Dubois

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.

Causes of unsuccessful ranibizumab treatment in exudative age-related macular degeneration in clinical settings.

Purpose: To identify the causes of loss of vision after ranibizumab therapy in patients with exudative age-related macular degeneration treated in three clinical settings. Methods: A retrospective multicentric analysis of 290 consecutive eyes comprising cohorts from 3 clinical settings showed that 21 eyes lost ≥15 letters on the Early Treatment Diabetic Retinopathy Study chart 1 year after the start of ranibizumab treatment. Fundus images of these eyes were analyzed by two independent readers to investigate the causes of visual loss. The three cohorts were compared. A search was made for factors predisposing to visual loss. A second analysis was performed to compare the baseline characteristics of patients who gained (visual acuity gainers) or lost (visual acuity losers) ≥15 letters. Results: Among the 290 eyes included, the proportions from each center experiencing visual loss were not significantly different (mean, 7.24%, P = 0.2631). Mean visual loss of affected eyes was 27 letters. There was no significant difference between these eyes and others as regards age and gender of patients, laterality, type of choroidal neovascularization, number of visits, or initial visual acuity. Visual loss was secondary to the progression of atrophy in eight eyes, fibrosis in five eyes, a combination of fibrosis and atrophy in three eyes, severe subretinal hemorrhage in three eyes, and retinal pigment epithelial tear in two eyes. A significant difference between visual acuity gainers and losers was observed for 2 parameters: age of patients, 80.9 ± 5.3 years in visual acuity losers versus 77.5 ± 7.3 years in visual acuity gainers (P = 0.0473) and visual acuity at diagnosis, respectively, 56.2 ± 11.2 versus 49.0 ± 12.0 (P = 0.0288). Conclusion: Although uncommon, visual loss may occur during ranibizumab treatment and is because of the natural course of age-related macular degeneration in most cases.

Photodynamic therapy for juxtafoveal choroidal neovascularization in myopic eyes

PURPOSE To report the results of photodynamic therapy in myopic patients with juxtafoveal choroidal neovascularization (CNV). DESIGN Interventional case series. METHODS Three consecutive myopic patients with juxtafoveal CNV were treated by photodynamic therapy with the same protocol as the one used to treat subfoveal CNV. Visual acuity was measured on Early Treatment Diabetic Retinopathy Study (ETDRS) charts by an independent observer. Fluorescein angiography was performed 6 and 12 weeks after photodynamic therapy and then every 12 weeks. RESULTS In all three patients, one treatment of photodynamic therapy using verteporfin resulted in the involution of the CNV and improvement in best-corrected visual acuity from 20/50 or 20/40 to 20/25 or more. No retreatment was required during follow-up, which lasted for 12 to 24 months (mean = 17 months). CONCLUSION Photodynamic therapy may be an effective treatment for juxtafoveal CNV in myopic eyes.

Is indocyanine green angiography still relevant

Indocyanine green angiography (ICGA) was introduced in the 1970s for imaging the choroidal circulation because the dye was known for its safety and because of its particular optical properties, that is, absorption of the near-infrared light, which may penetrate normal ocular pigments (for review of the basic properties of indocyanine green (ICG), and historical contributions to ICGA, see Flower et al). Indocyanine green angiography had many technical limitations because of the use of high-speed infrared black and white films and xenon flash lamps. The technique was about to be abandoned, when in the 1990s, it was simplified by the development of digital angiography, better filters, better optical alignment, synchronized flash, high-contrast video monitors, and cameras that were very sensitive to near-infrared light. At that time, various studies showed that ICGA allowed the visualization of occult choroidal neovascularization (CNV), the most frequent type of CNV complicating age-related macular degeneration (AMD). The ability of ICGA to locate occult CNV accurately, especially inside pigment epithelial detachments (PEDs), inaugurated a new era, in which an increasing number of CNV cases became eligible for laser photocoagulation, the only CNV treatment available at that time. Furthermore, the widespread use of ICGA allowed the description of a new method of imaging many chorioretinal diseases, and in many cases, this method improved the results of treatment. Technique of ICGA also improved with the use of scanning laser ophthalmoscopy (SLO). Indeed, interpretation of ICGA differs greatly among conventional fundus cameras and SLOs. Because of the lack of literature comparing the two techniques, the advantages and drawbacks of the twomethods will not be discussed in the present review. However, in our opinion, it is necessary to know which technique has been used to obtain ICGA pictures to avoid any misdiagnosis. A PubMed search showed that in peer review journals, the number of articles published whose title included ‘‘indocyanine green angiography (or videoangiography)’’ decreased between 1995 and 2010, despite the increasing number of articles published and referenced (Figure 1). In our center, the frequency of the use of ICGA in relation to all other imaging methods decreased from 10.05% in 2000 to 0.6% in 2009 (S. Y. Cohen, MD, PhD, unpublished data, 2011). It may therefore be appropriate at the present time to define the indications for ICGA, not only by recalling the indications previously described but also by distinguishing the applications that remain useful in present clinical practice for the diagnosis and/or management of various conditions. However, in the present review, therapies improved by ICG, such as ICG-mediated photothrombosis or ICG as an adjunct to vitreoretinal surgery, will not be discussed.

Spectral domain optical coherence tomography analysis of macular changes in tilted disk syndrome.

Purpose: To evaluate the prevalence of macular complications in tilted disk syndrome by spectral domain optical coherence tomography (OCT). Methods: A monocentric retrospective study of consecutive patients with tilted disk syndrome, whose eyes were examined by spectral domain OCT (Cirrus; Zeiss) and fundus photography. Results: Fifty consecutive patients (39 women and 11 men; age range, 41–96 years) with uni- or bilateral tilted disk syndrome were enrolled. All affected eyes (n = 92) were imaged by spectral domain OCT and fundus photography. Fluorescein and/or indocyanine green angiography were performed in 33 patients (66%). Macular anomalies or complications were observed in 71 eyes (77.1%). Specifically, retinal pigment epithelial changes were described in 34 eyes (36.9%), choroidal neovascularization in 24 eyes (26%), and macular serous retinal detachment in 16 eyes (17.3%). Epiretinal membrane in 9 eyes (9.7%), myopic foveoschisis in 5 eyes (5.4%), and lamellar macular hole in 3 eyes (3.2%) were also detected relatively frequently by spectral domain OCT. Surprisingly, fovea plana was observed in 5 eyes (5.4%). Eleven eyes, complicated by choroidal neovascularization, were treated with ranibizumab, with a mean visual gain of 7.9 letters on Early Treatment Diabetic Retinopathy Study chart. Conclusion: Tilted disk syndrome can be associated with potentially severe macular complications. Spectral domain OCT allowed the recognition of additional macular changes associated with tilted disk syndrome, such as epiretinal membranes, myopic foveoschisis, and fovea plana.

T-shaped pigmentary changes in tilted disk syndrome.

Purpose Many complications associated with tilted disk syndrome may occur in the area bordering on the inferior staphyloma, including macular pigmentary changes, choroidal neovascularization, macular serous retinal detachment, polypoidal choroidal vascular anomalies, and radially orientated chorioretinal folds. The purpose of the present article is to describe an additional complication, Tshaped pigmentary changes, orientated radially from the border of the inferior staphyloma, in eyes with tilted disk syndrome.. Methods Retrospective series of 6 eyes of 6 patients (3 men and 3 women) aged from 35 to 67 years. All eyes were studied by fluorescein angiography. Results All 6 eyes exhibited pigmentary changes located along the border of the staphyloma, and also radially to it, giving a particular T-shaped pattern of pigmentary changes. These changes were visible as either a linear strip or a triangular or oval-shaped area. Three eyes had a documented history of subretinal leakage that mimicked central serous chorioretinopathy, a well-known complication of tilted disk syndrome. Conclusions T-shaped pigmentary changes may develop in the course of tilted disk syndrome, and should be added to the list of this syndromes possible retinal complications. These changes may indicate the presence of chronic leakage in the area around the superior border of the inferior staphyloma (Eur J Ophthalmol 2009; 19: 876–9).

RETICULAR PSEUDODRUSEN ARE NOT A PREDICTIVE FACTOR FOR THE 1-YEAR RESPONSE TO INTRAVITREAL RANIBIZUMAB IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

Purpose: To investigate reticular pseudodrusen (RPD) as a potential baseline factor predictive of a poor 1-year response to intravitreal ranibizumab in eyes with neovascular age-related macular degeneration. Methods: Retrospective, monocentric case series including 98 consecutive naive neovascular age-related macular degeneration patients. Presence of RPD was assessed by two graders based on color, blue-light, fundus autofluorescence pictures, and spectral-domain optical coherence tomography. A correlation between the presence of RPD and the visual change was investigated. Other baseline characteristics studied in a monovariate and multivariate analysis were the following: age, gender, affected side, loading dose, type of neovascularization, presence of retinal pigment epithelial detachment >250 &mgr;m, subretinal or intraretinal fluid, blood over >50% of the lesion, and subfoveal choroidal thickness. Results: The presence of RPD was not associated with a visual change (P = 0.96), but with a thin subfoveal choroidal thickness at baseline (P < 0.0001). The monovariate analysis showed that the presence of blood at baseline was associated with visual gain (P = 0.007). Conclusion: The presence of RPD at baseline was not identified as a factor associated with a poor 1-year response to ranibizumab in eyes with neovascular age-related macular degeneration. Studies with a longer follow-up may be needed to assess the impact of RPD on the visual prognosis of eyes with neovascular age-related macular degeneration.

Age at Occurrence of Exudative Age-Related Macular Degeneration in a Clinical Setting: Difference between 1986 and 2006

Purpose: To our knowledge, there is no published study on the evolution of age of occurrence of exudative age-related macular degeneration (AMD). The present study was performed to test whether or not the average age of patients with newly diagnosed choroidal neovascularization (CNV) due to AMD has changed in a clinical setting during the past 20 years. Methods: Nonrandomized comparative case study. Charts and fluorescein angiograms of consecutive patients diagnosed in 1986 and 2006 in a tertiary care center were analyzed to identify differences in age, gender and type of CNV. Mann-Whitney’s nonparametric test was used to compare the statistical distribution of the parameters. χ2 or Fisher’s exact test was used for categorical variables. Results: 357 patients with CNV due to AMD, 79 in 1986, and 278 in 2006 were included. The patients diagnosed in 2006 were 4.7 years older than those diagnosed in 1986 (80.1 ± 8.9 vs. 75.4 ± 6.7 years, p < 0.0001). The main increase was in the percentage of patients over 85 years: 11.39% in 1986 versus 26.98% in 2006. There was no significant difference between the two groups as regards gender or type of CNV. Conclusions: In our clinical setting, the average age of patients with newly diagnosed exudative AMD increased significantly between 1986 and 2006. The fact that in the present series more than 1 out of 4 patients was over 85 may have a significant impact on the potential side effects of currently available treatments of exudative AMD.

PERIPAPILLARY RETINAL PIGMENT EPITHELIUM CHANGES IN AGE-RELATED MACULAR DEGENERATION.

Purpose: To describe peripapillary retinal pigment epithelium changes observed in patients with age-related macular degeneration (AMD) and evaluate their prevalence. Methods: This study is a prospective, monocentric, comparative case series including 104 consecutive patients with AMD, and 34 patients who are more than 60 years old and consulting for other conditions (control group). Color and fundus autofluorescence images centered on the optic disk were taken and graded by 2 independent readers from 0 to 4: 0, absent; 1, uneven background; 2, focal hyperautofluorescent dots and spots; 3, light reticular pattern; 4, dense reticular pattern. Statistical analysis was performed to correlate the presence of peripapillary retinal pigment epithelium changes with age, sex, and AMD subtype. Results: Peripapillary retinal pigment epithelium changes were observed in 76/104 AMD eyes (73.0%) and were significantly more frequent than in eyes with other conditions (14/34, 41.1%, P = 0.002), whereas groups did not differ for age (P = 0.14). Grade ≥2 peripapillary retinal pigment epithelium changes were more frequently observed in patients with AMD than in controls (41.3 vs. 17.6%, P = 0.013). No differences were found between patients with AMD having peripapillary retinal pigment epithelium changes and other patients for age distribution (P = 0.14), sex ratio (P = 0.34), or AMD type (P = 0.57). Conclusion: Peripapillary retinal pigment epithelium changes were more frequent in patients with AMD than in controls, and when present, they were of higher grade. Peripapillary retinal pigment epithelium changes significance is not yet understood and needs further evaluation.