Ramin Tadayoni

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.

Intravitreal triamcinolone for refractory pseudophakic macular edema

PURPOSE To evaluate the efficacy of intravitreal triamcinolone in refractory pseudophakic cystoid macular edema. DESIGN A prospective, interventional case series. METHODS Three eyes of three patients with longstanding pseudophakic cystoid macular edema following uncomplicated cataract surgery, refractory to any medication, were treated with 8 mg of intravitreal triamcinolone. All three eyes were evaluated before injection and throughout follow-up with the Early Treatment Diabetic Retinopathy Studys visual acuity chart, fluorescein angiography, and macular mapping using optical coherence tomography. RESULTS A month after intravitreal triamcinolone injection, a dramatic decrease in macular thickness was noted by optical coherence tomography in all three eyes (from a mean of 502-233 microm). Mean improvement in visual acuity was 3.7 Snellen lines. Two to 4 months after triamcinolone injection, however, the edema recurred in all cases, to the same degree as before the injection, combined with a decrease in vision. Two eyes underwent a second injection of triamcinolone, and macular thickness decreased, but the edema again recurred 3 months after injection. CONCLUSION Intravitreal injection of triamcinolone induces striking regression, within 1 month, of chronic refractory macular edema. This regression appears to be transient, however, even after a second injection.

Dissociated optic nerve fiber layer appearance of the fundus after idiopathic epiretinal membrane removal

PURPOSE To report the appearance of the fundus, that is seen frequently after removal of an idiopathic epiretinal membrane and which we refer to as the dissociated optic nerve fiber layer appearance. DESIGN Interventional, noncomparative retrospective case series. PARTICIPANTS One hundred consecutive patients with an epiretinal membrane who underwent pars plana vitrectomy and epiretinal membrane peeling in one eye. METHODS Only patients with an idiopathic epiretinal membrane or a membrane associated with a peripheral retinal tear, but without retinal detachment, were considered for this study. Sixty-one patients met these criteria for one eye. Preoperative and postoperative best-corrected visual acuity and preoperative and postoperative blue filter fundus photographs were reviewed. Histopathologic specimens of epiretinal membranes were available for 14 eyes. MAIN OUTCOME MEASURES The postoperative incidence of the dissociated optic nerve fiber layer appearance on blue filter photographs, visual acuity changes, and the presence of internal limiting membrane in epiretinal membrane specimens. RESULTS The postoperative incidence of this feature on blue filter fundus photographs was 43%. No difference was found between eyes with or without this feature concerning the average preoperative and postoperative best-corrected visual acuity or the average change in visual acuity. Internal limiting membrane was present in all 14 epiretinal membrane specimens available. Five of these 14 patients concerned exhibited a dissociated optic nerve fiber layer appearance and 9 did not. CONCLUSIONS The dissociated optic nerve fiber layer appearance occurred frequently after removal of an epiretinal membrane. As far as we know, this feature has not been previously reported. It consisted of numerous arcuate striae within the posterior pole in the direction of the optic nerve fibers and slightly darker than the surrounding retina. This feature had no functional effect noticeable by the patient and did not preclude good visual recovery. The small number of histologic samples and the impossibility of quantifying the area of internal limiting membrane peeled off did not allow us to supply proof that this feature is due to the extensive peeling of the internal limiting membrane, although this is the most likely hypothesis.

Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration

Background/aims Real-life anti-vascular endothelial growth factor (VEGF) therapy use in patients with wet age-related macular degeneration (wAMD) was assessed in a retrospective, observational study in Canada, France, Germany, Ireland, Italy, the Netherlands, UK and Venezuela. Methods Medical records of patients with wAMD, who started ranibizumab treatment between 1 January 2009 and 31 August 2009, were evaluated. Data were collected until the end of treatment and/or monitoring or until 31 August 2011. Results 2227 patients who received ≥1 anti-VEGF injection with a baseline visual acuity assessment and ≥1 postbaseline visual acuity assessment for the treated eye were evaluated. Visual acuity improved until about day 120; thereafter, visual acuity gains were not maintained. Mean change in visual acuity score from baseline to years 1 and 2 was +2.4 and +0.6 letters, respectively. Patients received a mean of 5.0 and 2.2 injections in the first and second year, respectively. There were substantial differences in visual outcomes and injection frequency between countries. More frequent visits and injections were associated with greater improvements in visual acuity. Conclusions In clinical practice, fewer injections are administered than in clinical trials. Anti-VEGF treatment resulted in an initial improvement in visual acuity; however, this was not maintained over time. Trial registration number NCT01447043.

Persistence of fundus fluorescence after use of indocyanine green for macular surgery

PURPOSE To investigate the possible persistence and characteristics of infrared fluorescence of the fundus for several months after surgery with intraocular injection of indocyanine green (ICG). DESIGN Interventional, noncomparative, prospective case series. PARTICIPANTS Seventeen patients operated on in our department with ICG injection into the vitreous cavity, who gave prior informed consent. METHODS After standard three-port pars plana vitrectomy and posterior vitreous detachment, 0.1 to 0.2 ml of an ICG solution at a concentration of 2.5 mg/ml was injected through a 5- micro m sterile filter over the posterior pole and left in place for 3 minutes. The stained internal limiting membrane was then peeled off. Patients had postoperative infrared fundus photographs at each consultation in our department. Follow-up ranged from 1 to 7 months. Visual acuity and any unexpected event were also recorded. MAIN OUTCOME MEASURES Postoperative infrared fluorescence of the fundus. RESULTS The day after surgery, no green ICG staining of the fundus was visible on biomicroscopy. However, infrared photography showed diffuse fluorescence of the fundus. At 1 and 3 postoperative months, infrared fundus photography showed an intensely fluorescent optic nerve disc. In patients with macular hole, the center of the macula also exhibited faint granular fluorescence. At 6 months postoperative or later, only the optic disc remained fluorescent, but the fluorescence was far less intense than at 3 months. Infrared photographs of the fellow eyes exhibited no fluorescence. Visual acuity improved or was unchanged compared with preoperative vision in 16 eyes and decreased by 1 line in 1 eye. CONCLUSIONS After intraoperative use of ICG for macular surgery, fluorescence of the optic disc and of the macular center after macular hole surgery persisted for months in all cases. ICG may accumulate in the macular pigment epithelium and optic nerve, raising the problem of the as yet unknown pharmacokinetics of ICG after intravitreous administration and of its long-term safety.

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.

Relationship between macular hole size and the potential benefit of internal limiting membrane peeling

Aim: To investigate the relationship between the size of macular holes and the possible benefit of internal limiting membrane (ILM) peeling. Methods: 84 consecutive cases of idiopathic macular hole followed up for at least 3 months were included in this retrospective study. Surgery comprised pars plana vitrectomy, peeling of any epiretinal membrane, 17% C2F6 (hexafluoroethane) gas filling and 10 days of positioning. 36 eyes had ILM peeling. The main outcome measure was the macular hole closure rate checked by optical coherence tomography. Results: The overall postoperative closure rate was 90.5%. For macular holes ⩾400 μm in diameter, the rate was 100% with ILM peeling versus 73.3% without (p = 0.015). For smaller macular holes, the rates were 100% in both groups. Postoperative gain in visual acuity was not significantly different in eyes with ILM peeling and those without. Conclusions: ILM peeling does not seem to be useful for macular hole <400 μm in diameter. Its likely benefit has to be investigated for larger macular hole sizes, for which the failure rate is higher.

CAPILLARY PLEXUS ANOMALIES IN DIABETIC RETINOPATHY ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Purpose: To analyze the foveal microvasculature in eyes with diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA) and fluorescein angiography (FA). Methods: In this retrospective study of 20 eyes of 14 patients with DR imaged using OCTA and FA, clinical features of DR such as microaneurysms, capillary nonperfusion areas, and intraretinal microvascular abnormalities were analyzed. Results: In the superficial plexus, a rarefaction of capillaries with capillary nonperfusion areas was present in all eyes. Some of these nonperfused areas were not detected on FA and were better delimited on OCTA. Conversely, in the deep plexus, capillary nonperfusion areas were seen only in 35% (7/20) of eyes, whereas DR led to an alteration of the normal capillary vortex pattern in all eyes. Only 62% of microaneurysms visualized on FA were detected by OCTA (P = 0.02). Intraretinal microvascular abnormalities were well detected by both FA and OCTA. Conclusion: Optical coherence tomography angiography allowed detecting DR anomalies in both superficial and deep capillary plexus in all eyes. The ability of OCTA to detect microaneurysms was lower than that of FA although its accuracy for assessing capillary nonperfusion was better and may enable a proper grading of DR progression.

TREAT-AND-EXTEND REGIMENS WITH ANTI-VEGF AGENTS IN RETINAL DISEASES: A Literature Review and Consensus Recommendations.

Purpose: A review of treat-and-extend regimens (TERs) with intravitreal anti–vascular endothelial growth factor agents in retinal diseases. Methods: There is a lack of consensus on the definition and optimal application of TER in clinical practice. This article describes the supporting evidence and subsequent development of a generic algorithm for TER dosing with anti–vascular endothelial growth factor agents, considering factors such as criteria for extension. Results: A TER algorithm was developed; TER is defined as an individualized proactive dosing regimen usually initiated by monthly injections until a maximal clinical response is observed (frequently determined by optical coherence tomography), followed by increasing intervals between injections (and evaluations) depending on disease activity. The TER regimen has emerged as an effective approach to tailoring the dosing regimen and for reducing treatment burden (visits and injections) compared with fixed monthly dosing or monthly visits with optical coherence tomography–guided regimens (as-needed or pro re nata). It is also considered a suitable approach in many retinal diseases managed with intravitreal anti–vascular endothelial growth factor therapy, given that all eyes differ in the need for repeat injections. Conclusion: It is hoped that this practical review and TER algorithm will be of benefit to health care professionals interested in the management of retinal diseases.

NEW INSIGHT INTO THE MACULAR DEEP VASCULAR PLEXUS IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Purpose: To describe the macular deep capillary plexus (DCP) in normal eyes using optical coherence tomography angiography. Methods: Retrospective study including 41 consecutive normal eyes imaged using optical coherence tomography angiography (RTVue XR Avanti; Optovue Inc). Default autosegmentation of the superficial capillary plexus (SCP) and DCP, and manual adjustments of “deep settings” were used to analyze the organization of the normal macular microvascularization and to investigate in vivo the connection between these capillary networks. Results: Mean age was 31 years (range, 22–55 years). The SCP and DCP had 2 different organizations, but the plexus autosegmentation was imperfect: In 68% of cases, the image of the SCP variably superimposed on the DCP, interfering with its analysis. The SCP was composed on average of 7 pairs of arterioles and venules obvious on each 3-mm × 3-mm optical coherence tomography angiography scanning area. The DCP was composed of a capillary vortex arrangement, whose centers were aligned along the course of the macular superficial venules. Conclusion: The SCP and DCP had two different topographic organizations. The pattern of the capillary units converging into capillary vortexes highly suggests that they drain into the superficial venules. The different structural properties of the SCP and DCP could explain the differences in flow resistance and perfusion.