Ali Dirani

Central serous chorioretinopathy: Recent findings and new physiopathology hypothesis

Central serous chorioretinopathy (CSCR) is a major cause of vision threat among middle-aged male individuals. Multimodal imaging led to the description of a wide range of CSCR manifestations, and highlighted the contribution of the choroid and pigment epithelium in CSCR pathogenesis. However, the exact molecular mechanisms of CSCR have remained uncertain. The aim of this review is to recapitulate the clinical understanding of CSCR, with an emphasis on the most recent findings on epidemiology, risk factors, clinical and imaging diagnosis, and treatments options. It also gives an overview of the novel mineralocorticoid pathway hypothesis, from animal data to clinical evidences of the biological efficacy of oral mineralocorticoid antagonists in acute and chronic CSCR patients. In rodents, activation of the mineralocorticoid pathway in ocular cells either by intravitreous injection of its specific ligand, aldosterone, or by over-expression of the receptor specifically in the vascular endothelium, induced ocular phenotypes carrying many features of acute CSCR. Molecular mechanisms include expression of the calcium-dependent potassium channel (KCa2.3) in the endothelium of choroidal vessels, inducing subsequent vasodilation. Inappropriate or over-activation of the mineralocorticoid receptor in ocular cells and other tissues (such as brain, vessels) could link CSCR with the known co-morbidities observed in CSCR patients, including hypertension, coronary disease and psychological stress.

Factors Influencing the Treatment Response of Pigment Epithelium Detachment in Age-Related Macular Degeneration

PURPOSE To study the effect of various baseline factors, particularly the type of drug (ranibizumab vs aflibercept), on the functional and anatomic response of treatment-naïve pigment epithelial detachment (PED) associated with neovascular age-related macular degeneration (neovascular AMD), after 3 intravitreal injections. DESIGN Retrospective consecutive case series. METHODS This study included 102 patients (n = 115 eyes) with treatment-naïve neovascular AMD and PED (>150 μm), who were treated with either ranibizumab (n = 68 eyes) or aflibercept (n = 47 eyes). A multivariate analysis using stepwise linear regression was performed in order to assess factors influencing visual acuity improvement, as well as treatment response of PED height after 3 monthly injections. RESULTS Multivariate analysis revealed that better visual improvement was associated with lower best-corrected visual acuity (BCVA) at baseline (P = .001), presence of subretinal fluid (P = .001), and retinal angiomatous proliferation (P = .001); PED reduction was associated with higher PED at baseline (P = .001), predominantly serous PED (P = .003), and the use of aflibercept (P = .022). Drug type was not associated with change in BCVA at 3 months. CONCLUSION Eyes with neovascular AMD and PED showed significant functional and anatomic response after 3 monthly intravitreal anti-VEGF injections. The functional response depended on baseline BCVA, presence of subretinal fluid, and retinal angiomatous proliferation, while anatomic response was influenced by baseline PED height, degree of vascularization, and drug type. Drug type was not associated with change in BCVA, but had a weak effect on anatomic response.

Resolution of foveal detachment in dome-shaped macula after treatment by spironolactone: report of two cases and mini-review of the literature.

Dome-shaped macula (DSM) was recently described in myopic patients as a convex protrusion of the macula within a posterior pole staphyloma. The pathogenesis of DSM and the development of associated serous foveal detachment (SFD) remain unclear. The obstruction of choroidal outflow and compressive changes of choroidal capillaries have been proposed as causative factors. In this paper, we report two cases of patients with chronic SFD associated with DSM treated with oral spironolactone. After treatment, there was a complete resolution of SFD in both patients. To the best of our knowledge, this is the first report of successful treatment of SFD in DSM by a mineralocorticoid receptor antagonist.

Safety and Visual Outcome of Visian Toric ICL Implantation after Corneal Collagen Cross-Linking in Keratoconus: Up to 2 Years of Follow-Up

Purpose. To evaluate the long-term safety and clinical outcome of phakic Visian toric implantable collamer lens (ICL) insertion after corneal collagen cross-linking (CXL) in progressive keratoconus. Methods. This was a retrospective study of 30 eyes (19 patients), with progressive keratoconus, who underwent sequential CXL followed by Visian toric ICL implantation after 6 months. Results. At baseline, 6 eyes had stage I, 14 eyes stage II, and 10 eyes stage III keratoconus graded by Amsler-Krumeich classification. At 6 months after CXL, only K (steep) and K (max) decreased significantly from baseline, with no change in visual acuity or refraction. Flattening in keratometric readings was stable thereafter. There was significant improvement in mean uncorrected distance visual acuity (1.57 ± 0.56 to 0.17 ± 0.06 logMAR, P < 0.001) and mean corrected distance visual acuity (0.17 ± 0.08 to 0.11 ± 0.05 logMAR, P < 0.001) at 12 months after ICL implantation that was maintained at the 2-year follow-up. Mean cylinder power and mean spherical equivalent (SE) also decreased significantly after ICL implantation. A small hyperopic shift in SE (+0.25 D) was observed at 2 years that did not alter visual outcomes. Conclusions. Visian toric ICL implantation following CXL is an effective option for improving visual acuity in patients with keratoconus up to 2 years.

The effect of switching ranibizumab to aflibercept in refractory cases of macular edema secondary to ischemic central vein occlusion.

BACKGROUND Macular edema resulting from central retinal vein occlusion is effectively treated with anti-vascular endothelial growth factor injections. However, some patients need monthly retreatment and still show frequent recurrences. The purpose of this study was to evaluate the visual and anatomic outcomes of refractory macular edema resulting from ischemic central retinal vein occlusion in patients switched from ranibizumab to aflibercept intravitreal injections. PATIENTS AND METHODS We describe a retrospective series of patients followed in the Medical Retina Unit of the Jules Gonin Eye Hospital for macular edema due to ischemic central retinal vein occlusion, refractory to monthly retreatment with ranibizumab, and changed to aflibercept. Refractory macular edema was defined as persistence of any fluid at each visit one month after last injection during at least 6 months. All patients had to have undergone pan-retinal laser scan. RESULTS Six patients were identified, one of whom had a very short-term follow-up (excluded from statistics). Mean age was 57±12 years. The mean changes in visual acuity and central macular thickness from baseline to switch were +20.6±20.3 ETDRS letters and -316.4±276.6 µm, respectively. The additional changes from before to after the switch were +9.2±9.5 ETDRS letters and -248.0±248.7 µm, respectively. The injection intervals could often be lengthened after the switch. CONCLUSIONS Intravitreal aflibercept seems to be a promising alternative treatment for macular edema refractory to ranibizumab in ischemic central retinal vein occlusion.

Non-topography–guided PRK Combined With CXL for the Correction of Refractive Errors in Patients With Early Stage Keratoconus

PURPOSE To evaluate the safety and clinical outcome of combined non-topography-guided photorefractive keratectomy (PRK) and corneal collagen cross-linking (CXL) for the treatment of mild refractive errors in patients with early stage keratoconus. METHODS A retrospective, nonrandomized study of patients with early stage keratoconus (stage 1 or 2) who underwent simultaneous non-topography-guided PRK and CXL. All patients had at least 2 years of follow-up. Data were collected preoperatively and postoperatively at the 6-month, 1-year, and 2-year follow-up visit after combined non-topography-guided PRK and CXL. RESULTS Seventy-nine patients (140 eyes) were included in the study. Combined non-topography-guided PRK and CXL induced a significant improvement in both visual acuity and refraction. Uncorrected distance visual acuity significantly improved from 0.39 ± 0.22 logMAR before combined non-topography-guided PRK and CXL to 0.12 ± 0.14 logMAR at the last follow-up visit (P <.001) and corrected distance visual acuity remained stable (0.035 ± 0.062 logMAR preoperatively vs 0.036 ± 0.058 logMAR postoperatively, P =.79). The mean spherical equivalent decreased from -1.78 ± 1.43 to -0.42 ± 0.60 diopters (D) (P <.001), and the mean cylinder decreased from 1.47 ± 1.10 to 0.83 ± 0.55 D (P <.001). At the last follow-up visit mean keratometry flat was 43.30 ± 1.75 vs 45.62 ± 1.72 D preoperatively (P = .03) and mean keratometry steep was 44.39 ± 3.14 vs 46.53 ± 2.13 D preoperatively (P = .02). Mean central corneal thickness decreased from 501.74 ± 13.11 to 475.93 ± 12.25 µm following combined non-topography-guided PRK and CXL (P < .001). No intraoperative complications occurred. Four eyes developed mild haze that responded well to a short course of topical steroids. No eye developed infectious keratitis. CONCLUSIONS Combined non-topography-guided PRK and CXL is an effective and safe option for correcting mild refractive error and improving visual acuity in patients with early stable keratoconus.

CONVERSION TO AFLIBERCEPT THERAPY VERSUS CONTINUING WITH RANIBIZUMAB THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION DEPENDENT ON MONTHLY RANIBIZUMAB TREATMENT.

Purpose: To compare the effects of converting to aflibercept therapy with continuing ranibizumab therapy in eyes with neovascular age-related macular degeneration requiring monthly ranibizumab treatment. Methods: Patients were selected from the 104 patients (115 eyes) already enrolled in an “Observe and Plan” prospective case series that included treating neovascular age-related macular degeneration with ranibizumab for 24 months. Patients who still needed monthly retreatment at the end of a 2-year study were randomized to either continue ranibizumab therapy or to convert to aflibercept therapy. Outcome measures included average interval between treatments, resolution of exudative signs, number of retreatments, and change in visual acuity over 12 months (the third treatment year). Results: Nineteen patients (21 eyes) met the inclusion criteria. Ten eyes were randomized to receive aflibercept, and 11 eyes remained on ranibizumab. Groups were balanced for baseline characteristics. Outcomes were similar in the 2 groups over a 12-month study duration, with no statistical difference. Conclusion: This comparative pilot study suggests that neovascular age-related macular degeneration requiring monthly retreatment with ranibizumab may respond in similar ways to both ranibizumab and aflibercept treatment. Larger sample sizes would be needed to confirm this observation.

Long-term follow-up of choroidal neovascularization in pathological myopia treated with intravitreal ranibizumab.

BACKGROUND The purpose of this contribution is to report our functional results on the efficacy of intravitreal ranibizumab for submacular choroidal neovessels (CNV) in high myopia, and to compare the roles of optical coherence tomography (OCT), fluorescein angiography and visual acuity changes in the treatment decision prior to each injection. PATIENTS AND METHODS This is a retrospective study performed in Jules Gonin Eye Hospital. It included all patients with myopic CNV treated with intravitreal ranibizumab injections with a minimum follow-up of 24 months. After an induction dosing from 1 to 3 injections, the follow-up was based on a pro re nata regimen. Ophthalmic evaluation, best corrected visual acuity, and OCT were done at each visit, and fluorescein angiography at baseline and if neovascular activity was suspected. Retreatment criteria included metamorphopsia, visual loss of ≥5 ETDRS letters, any fluid on OCT and/or leakage on fluorescein angiography. RESULTS 24 eyes were included in the study. Mean follow-up was 49 months. Mean visual acuity improved significantly from 62.8±13.8 letters at baseline to 72.8±12.9 letters at last follow-up visit (p=0.001). The mean number of injections was 2.2 in the first year and below 1 for the following years. The sensitivities of fluorescein angiography, SD OCT, and visual acuity loss≥5 letters were 62.6%, 51.4%, and 40%, respectively. The fluorescein angiography showed a significantly higher sensitivity in treatment decision than OCT (p=0.007). CONCLUSION Our study has shown that ranibizumab injections provide a significant long-term visual benefit in myopic CNV with a small number of injections. Fluorescein angiography has a preponderant role in the treatment decision of active myopic CNV.

REFRACTORY INTRARETINAL OR SUBRETINAL FLUID IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TREATED WITH INTRAVITREAL RANIZUBIMAB: Functional and Structural Outcome.

Purpose: To investigate the visual acuity results of eyes with neovascular age-related macular degeneration and refractory fluid despite monthly treatment with ranibizumab, and to investigate differences between refractory subretinal fluid and intraretinal cystic changes. Methods: Retrospective chart review of consecutive treatment-refractory neovascular age-related macular degeneration, defined as persistent intraretinal or subretinal fluid despite monthly ranibizumab injections during 12 months or more. Data were evaluated for baseline characteristics, type and location of the refractory fluid, mean visual acuity change, number of injections, and the time point of first complete disappearance of all fluid on spectral domain optical coherence tomography. Results: Seventy-six eyes (74 patients, mean age, 76.8 years) were identified. The mean follow-up was 33.6 months (range, 12–73 months). The mean number of injections was 11.4 in the first year and 27.7 over follow-up. The refractory fluid was located subfoveally in 61.8%. In 27 eyes (35.5%), the fluid resolved after a mean of 21.8 months (range, 13–49 months). Mean visual acuity increased by 9.0, 7.9, and 7.9 letters by Month 12, Month 24, and Month 36, respectively. Subgroup analysis revealed a higher risk for fibrosis (odds ratio, 3.30) or atrophy (odds ratio, 3.34) in patients with refractory cysts as compared with refractory subretinal fluid. Furthermore, refractory cysts showed a higher risk for a 10-letter visual acuity loss (P = 0.018). Conclusion: Fluid refractory to monthly treatment with ranibizumab for neovascular age-related macular degeneration still allowed for well-maintained visual improvement, even in subfoveal location. Late fluid resolution may occur. However, refractory cysts were associated with poorer anatomical and functional outcome than subretinal fluid.

Pigment epithelial detachment response to aflibercept in neovascular age-related macular degeneration refractory to ranibizumab: time course and drug effects

Purpose: To investigate the time course of pigment epithelium detachment (PED) height and its change after anti–vascular endothelial growth factor switch from ranibizumab to aflibercept in neovascular age-related macular degeneration. Methods: This retrospective study included 60 eyes of 50 consecutive patients with neovascular age-related macular degeneration who showed refractory intraretinal or subretinal fluid (≥9 months) despite monthly ranibizumab treatment and an associated PED (height ≥150 &mgr;m). The treatment was switched to aflibercept, and patients were followed-up for at least 9 months. Data on the height and type of PED, exudative fluid, and best-corrected visual acuity were collected at four different time points (two before and two after the drug switch). Results: The maximal PED height was significantly decreased over time, both under ranibizumab and aflibercept treatment. However, the reduction was significantly greater during the 3 months after the switch to aflibercept, due to two outliers. Visual acuity remained stable. Complete resolution of intraretinal or subretinal fluid was observed in 9 cases (15%) at 3 months after switch, allowing for treatment interval extension. Conclusion: Maximal PED height continuously decreased over time. Switching the intravitreal anti–vascular endothelial growth factor medication from ranibizumab to aflibercept had a significantly stronger short-term effect on PED height reduction, without changes in visual acuity.