CYSTOID MACULAR EDEMA IN BIRDSHOT RETINOCHOROÏDITIS: Long-Term Treatment Study in 142 Patients.

PURPOSE: To assess the long-term efficacy and safety of treatments for cystoid macular edema in birdshot retinochoroïditis. METHODS: Observational retrospective study of 142 HLA-A29-positive patients with cystoid macular edema; the main outcome was the optical coherence tomography intraretinal cysts resolution. RESULTS: During the mean follow-up of 75 months (12-178), 61.3% of patients were successfully treated using 1 to 3 treatment steps, while the others needed more steps. At 6 months, there were no significant effects on ME for anti-TNF (tumor necrosis factor) and IVIg (immunoglobulin) in contrast to antimetabolites (OR 1.98), systemic GCS (glucocorticosteroids), CsA (cyclosporine A) and tocilizumab (odds ratio closed to 2.7), intraocular injected GCS (odds ratio of 4.2), and interferon (odds ratio of 4.4). The percentages of therapeutic success trend to decrease from the initial three treatment steps to the subsequent treatment steps, for systemic GCS (84% to 70%), for anti-TNF (42% to 33%), and for CsA (71% to 33%); the success percentages did not decrease for injected GCS (83% to 89%). Macular edema recurrence occurred with the highest percentage for injected GCS (86.8%, P = 0.01) and the lowest for tocilizumab (10.5%, P = 0.001). Interferons-α and tocilizumab were associated with the lowest prednisone daily doses. CONCLUSION: The classical uveitic cystoid macular edema therapeutic algorithm could be adapted to birdshot retinochoroïditis.

ROSAH syndrome mimicking chronic uveitis.

To suggest a unique missense variant candidate based on long-term ophthalmological changes and associated systemic signs described in five patients from two unrelated families affected by an autosomal dominant multi-systemic disorder including Retinal dystrophy, Optic nerve oedema, Splenomegaly, Anhidrosis and migraine Headaches, called ROSAH syndrome, related to a unique missense variant in ALPK1 gene. Observational longitudinal follow-up study of unrelated families. Clinical analysis of ophthalmological and systemic examinations was performed, followed by genetic analysis, including targeted Next Generation Sequencing (NGS) and Whole-Genome Sequencing (WGS). The ophthalmological phenotype showed extensive optic nerve swelling associated with early macular oedema and vascular leakage. The main associated systemic manifestations were recurrent fever, splenomegaly, anhidrosis, mild cytopenia, anicocytosis and hypersegmented polynuclear cells. WGS, shortened in the second family by the gene candidate suggestion, revealed in all patients the heterozygous missense variant c.710C>T; p.(Thr237Met) in ALPK1. The primary morbidity in ROSAH syndrome in this cohort appeared ophthalmological. Comprehensive, detailed phenotype changes aided by the advancement in genetic testing could allow an early genetic diagnosis of ROSAH syndrome and targeted treatment. The unique missense variant may be suggested as a target of gene correction therapy.

Severe macular complications in glaucoma: high-resolution multimodal imaging characteristics and review of the literature.

PURPOSE: To describe imaging characteristics of severe macular complications occurring in glaucoma and discuss available treatments. METHODS: Retrospective case series of glaucomatous patients with macular retinoschisis (MR) and/or serous retinal detachment (SRD). Patients underwent a complete ophthalmological examination and multimodal imaging including retinography, SD-OCT, fluorescein and indocyanine green angiography (FA & ICGA) and adaptive optics (AO). RESULTS: Ten eyes (8 patients) were included. Initial BCVA was 1.04 ± 1.12 logMAR and IOP was 24.0 ± 9.3mmHg. All eyes presented with MR while SRD was present in 5 eyes (5 patients), with a central macular thickness of 573 ± 152 µm. FA and ICGA allowed to exclude leakage in all cases. A focal lamina cribrosa defect (LCD) was found in four eyes (4 patients) using OCT, with AO providing en-face visualization of the defect in one eye. Outer retinal hole was present in 3 eyes (3 patients). No visual improvement or resolution of the macular retinoschisis was observed in eyes with medical or surgical IOP control (N = 9). Vitrectomy with internal membrane limiting peeling and gas tamponade was performed in one eye with good visual results. CONCLUSIONS: Multimodal high-resolution imaging is essential to diagnose severe macular complications associated with advanced glaucoma.

Casitas B-lineage lymphoma Gene Mutation Ocular Phenotype.

This article describes the ocular phenotype associated with the identified Casitas B-lineage lymphoma (CBL) gene mutation and reviews the current literature. This work also includes the longitudinal follow-up of five unrelated cases of unexplained fundus lesions with visual loss associated with a history of hepatosplenomegaly. Wide repeated workup was made to rule out infections, inflammatory diseases, and lysosomal diseases. No variants in genes associated with retinitis pigmentosa, cone-rod dystrophy, and inherited optic neuropathy were found. Molecular analysis was made using next-generation sequencing (NGS) and whole-exome sequencing (WES). The results included two cases sharing ophthalmological signs including chronic macular edema, vascular leakage, visual field narrowing, and electroretinography alteration. Two other cases showed damage to the optic nerve head and a fifth young patient exhibited bilateral complicated vitreoretinal traction and carried a heterozygous mutation in the CBL gene associated with a mutation in the IKAROS gene. Ruxolitinib as a treatment for RASopathy did not improve eye conditions, whereas systemic lesions were resolved in one patient. Mutations in the CBL gene were found in all five cases. In conclusion, a detailed description may pave the way for the CBL mutation ocular phenotype. Genetic analysis using whole-exome sequencing could be useful in the diagnosis of unusual clinical features.

Efficacy and Safety of Intravitreal Sirolimus for Noninfectious Uveitis of the Posterior Segment: Results from the Sirolimus Study Assessing Double-Masked Uveitis Treatment (SAKURA) Program.

PURPOSE: To evaluate the efficacy and safety of intravitreal sirolimus in the management of noninfectious uveitis of the posterior segment (NIU-PS). DESIGN: Combined analysis of 2 phase 3, randomized, double-masked, multinational, 6-month studies. PARTICIPANTS: Adults with active NIU-PS (intermediate uveitis, posterior uveitis, or panuveitis; defined as vitreous haze [VH] ≥1.5+ on modified Standardization of Uveitis Nomenclature scale). METHODS: Patients were randomized 1:1:1 to receive intravitreal sirolimus 44 µg (n = 208), 440 µg (n = 208), or 880 µg (n = 177) on days 1, 60, and 120. Patients discontinued medications for NIU-PS except for systemic corticosteroids, which were tapered according to protocol. Enrollment in the 880-µg group was terminated after interim results found no significant difference in efficacy compared with the 440-µg dose. MAIN OUTCOME MEASURES: The primary efficacy end point was the percentage of patients with VH of 0 at month 5 in the study eye without the use of rescue therapy. Secondary efficacy end points included VH of 0 or 0.5+, corticosteroid-tapering success, and changes in best-corrected visual acuity (BCVA). Safety measures included ocular and nonocular adverse events. RESULTS: A total of 592 patients were randomized. Significantly higher proportions of patients treated with 440 µg compared with 44 µg intravitreal sirolimus achieved VH of 0 (21.2% vs. 13.5%; P = 0.038) and VH of 0 or 0.5+ (50.0% vs. 40.4%; P = 0.049) at month 5. Best-corrected visual acuity was stable (absolute change <5 ETDRS letters) or improved >5 letters in 80.1% and 80.2% of patients in the 440-µg and 44-µg groups, respectively. At month 5, corticosteroids were tapered successfully in 69.6% and 68.8% of patients in the 440-µg and 44-µg groups, and among these patients, VH of 0 or 0.5+ was achieved by 43.5% and 28.1% in the 440-µg and 44-µg groups. Both doses were generally well tolerated. Mean changes from baseline intraocular pressure (IOP) in the study eye at each analysis visit were minimal in all treatment groups. CONCLUSIONS: Intravitreal sirolimus 440 µg improved ocular inflammation, as measured by VH, compared with the 44-µg dose, with minimal impact on IOP, while preserving BCVA.

Evaluation of outer retinal tubulations in eyes switched from intravitreal ranibizumab to aflibercept for treatment of exudative age-related macular degeneration.

PURPOSE: To evaluate the changes of outer retinal tubulations (ORTs) as seen on spectral-domain optical coherence tomography (SD OCT) in eyes with neovascular age-related macular degeneration (AMD) where treatment was switched from intravitreal ranibizumab to intravitreal aflibercept. METHODS: This was a prospective study of eyes diagnosed with neovascular AMD and previously treated with >6 intravitreal ranibizumab injections and switched to aflibercept, conducted at a single centre (Department of Ophthalmology at Pitié Salpetriere Hospital, Paris VI University) from January to July 2015. Before and after treatment was switched from ranibizumab to aflibercept, SD-OCT was used to evaluate the presence of ORTs. Additional assessments in this patient group included best-corrected visual acuity (BCVA), fluorescein angiography (FA), indocyanine green angiography (ICGA). Changes in pigment epithelium detachments (PED), presence of intraretinal cysts, and presence of subretinal fluid (SRF) were also noted. RESULTS: Twenty-four eyes of 24 consecutive patients (15 female/nine male, mean age 70 years) diagnosed with neovascular AMD and previously treated with >6 intravitreal ranibizumab injections and switched to aflibercept were included in the analysis. After receiving aflibercept, patients were followed for a mean of 6.1 months. Prior to treatment switch, 97 % of eyes showed ORTs, while after treatment switch to aflibercept, at the end of the study period, 75 % had ORTs (p = 0.219). Changes in BCVA (LogMAR) were not statistically significant (1.16 ± 0.44 to 1.18 ± 1.06, p = 0.12), however, a significant reduction in central macular thickness (CMT) (from 406 µm ± 112 to 263 µm ± 68, p = 0.001), PED (from 70.8 % to 41.7 % , p = 0.016), presence of intraretinal cysts (from 83.3 % to 33.3 %, p = 0.002) and SRF (from 91.7 % to 25 %, p = 0.001 ) were noted. CONCLUSION: After switching from ranibizumab treatment to aflibercept, ORTs remained present in 75 % of eyes, and significant reductions in CMT, PED, and SRF, and presence of intraretinal cysts were observed.

Intravitreal Sirolimus for Noninfectious Uveitis: A Phase III Sirolimus Study Assessing Double-masKed Uveitis TReAtment (SAKURA).

PURPOSE: To evaluate the efficacy and safety of intravitreal sirolimus in the treatment of noninfectious uveitis (NIU) of the posterior segment (i.e., posterior, intermediate, or panuveitis). DESIGN: Phase III, randomized, double-masked, active-controlled, 6-month study with intravitreal sirolimus. PARTICIPANTS: Adults with active NIU of the posterior segment (intermediate, posterior, or panuveitis), defined as a vitreous haze (VH) score >1+. Subjects discontinued NIU medications before baseline, except for systemic corticosteroids, which were allowed only for those already receiving them at baseline and were rapidly tapered after baseline per protocol. METHODS: Intravitreal sirolimus assigned 1:1:1 at doses of 44 (active control), 440, or 880 µg, administered on Days 1, 60, and 120. MAIN OUTCOME MEASURES: The primary efficacy outcome was the percentage of subjects with VH 0 response at Month 5 (study eye) without use of rescue therapy. Secondary outcomes at Month 5 were VH 0 or 0.5+ response rate, corticosteroid tapering success rate (i.e., tapering to a prednisone-equivalent dosage of ≤5 mg/day), and changes in best-corrected visual acuity (BCVA). Adverse events during the double-masked treatment period are presented. RESULTS: A total of 347 subjects were randomized. Higher proportions of subjects in the intravitreal sirolimus 440 µg (22.8%; P = 0.025) and 880 µg (16.4%; P = 0.182) groups met the primary end point than in the 44 µg group (10.3%). Likewise, higher proportions of subjects in the 440 µg (52.6%; P = 0.008) and 880 µg (43.1%; P = 0.228) groups achieved a VH score of 0 or 0.5+ than in the 44 µg group (35.0%). Mean BCVA was maintained throughout the study in each dose group, and the majority of subjects receiving corticosteroids at baseline successfully tapered off corticosteroids (44 µg [63.6%], 440 µg [76.9%], and 880 µg [66.7%]). Adverse events in the treatment and active control groups were similar in incidence, and all doses were well tolerated. CONCLUSIONS: Intravitreal sirolimus 440 µg demonstrated a significant improvement in ocular inflammation with preservation of BCVA in subjects with active NIU of the posterior segment.

Anatomic and functional prognosis of vitreoretinal surgery in rhegmatogenous retinal detachment associated with intraocular inflammation.

BACKGROUND/OBJECTIVES: The predictive factors of surgical results in uveitic retinal detachment (RD) are lacking. The objective was to study the surgical outcomes and determine the risk factors for surgical failure in rhegmatogenous RD associated with intraocular inflammation (RRDIOI). METHODS: Retrospective series of consecutive eyes with RRDIOI undergoing vitreoretinal surgery between 2012 and 2019 in two French referral centres. Patients underwent 23- or 25 G pars plana vitrectomy (PPV), scleral buckling (SB), or a combination of both. The main objective was to describe the predictive factors of visual recovery and anatomical success after surgery. RESULTS: Seventy-one eyes were included. Posterior and panuveitis accounted for 91.5% of eyes. Seventy-five percent of eyes had an infectious cause for their uveitis. The first surgery consisted in PPV alone, SB alone, or both in 87.3%, 4.2% and 8.5% of cases respectively. The reattachment rate was 74.6% after one surgery (100% in case of SB, either alone or in association with PPV). On multivariate analysis, the only predictive factor of visual improvement was a baseline BCVA ≥ 20/400, while the only predictive factor for surgical success at 12 months was the absence of RD recurrence within the first 6 weeks of surgery. CONCLUSIONS: RRDIOI has a relatively favourable anatomical prognosis. The addition of scleral buckling may be beneficial in selected cases.

Ocular Toxocariasis in Adult Caucasian Patients: Clinical Presentations and Treatment Outcomes.

PURPOSE: To report the clinical features and treatment outcomes in adult Caucasians with ocular toxocariasis (OT) and investigate their prognosis depending on their serological status. METHODS: Retrospective observational cohort study (2016-2021) including consecutive adults with uveitis and positive western blot (WB) in the aqueous humor or vitreous. The presence of serum antibodies was not necessary for inclusion, allowing to compare the outcomes depending on the serological status. RESULTS: Seventeen eyes of 15 patients were included. Mean age at diagnosis was 51.9 years. Vitreous inflammation was the most frequent sign (100%). Vitreoretinal tractions (41.2%) and chorioretinal granulomas (58.8%) were less prevalent. Atypical features were: spontaneous intravitreal hemorrhage (23.5%), exudative retinal detachment (11.8%), isolated macular edema (17.6%), papillitis (29.4%) and vasculitis (47.1%). Twenty percent of patients had a positive serum serology. Baseline clinical features did not differ statistically depending on the serological status; however, the degree of inflammation was numerically higher in patients with negative serology. Overall, macular thickness, anterior and posterior segment inflammation improved significantly after treatment with oral albendazole, systemic ± local corticosteroids. Vitrectomy (47.1%) was performed in case of persistent vitritis (62.5%), retinal detachment (12.5%) and intravitreous hemorrhage (25%). CONCLUSION: OT has no pathognomonic sign and atypical presentations were not infrequent in this adult Caucasian cohort. Serum antibodies were rarely positive, stressing on the importance of ocular sample analysis, especially in case of atypical features. Serum antibodies may prove useful in forecasting the rapidity of inflammation clearance. Antiparasitic and anti-inflammatory treatment was safe and efficient in most cases.

Methotrexate versus conventional disease-modifying antirheumatic drugs in the treatment of non-anterior sarcoidosis-associated uveitis.

AIMS: To compare the safety and efficacy of methotrexate (MTX), mycophenolate mofetil (MMF) and azathioprine (AZA) in non-anterior sarcoidosis-associated uveitis. METHODS: Retrospective study including non-anterior sarcoidosis-associated uveitis according to the revised International Workshop on Ocular Sarcoidosis criteria. The primary outcome was defined as the median time to relapse or occurrence of serious adverse events leading to treatment discontinuation. RESULTS: 58 patients with non-anterior sarcoidosis-associated uveitis (MTX (n=33), MMF (n=16) and AZA (n=9)) were included. The time to treatment failure (ie, primary outcome) after adjustment for corticosteroids dose and the presence of vasculitis was significantly higher with MTX (median time of 34.5 months with MTX (IQR: 11.8 -not reached) vs 8.4 months (3.1-22.9) with MMF and 16.8 months (8.0-90.1) with AZA (p=0.020)). The risk of relapse at 12 months was more than twice lower in MTX as compared with MMF (p=0.046). Low visual acuity at the last visit was significantly lower with MTX (4% vs 9% in MMF vs 57% in AZA group (p=0.008)). Regarding all 75 lines of treatment (MTX (n=39), MMF (n=24) and AZA (n=12)), MTX was more effective than MMF and AZA to obtain treatment response at 3 months (OR 10.85; 95% CI 1.13 to 104.6; p=0.039). Significant corticosteroid-sparing effect at 12 months (p=0.035) was only observed under MTX. Serious adverse events were observed in 6/39 (15%), 5/24 (21%) and 2/12 (17%) with MTX, MMF and AZA, respectively. CONCLUSION: In non-anterior sarcoidosis-associated uveitis, MTX seems to be more efficient compared with AZA and MMF and with an acceptable safety profile.

TARGET: A phase I/II open-label multicenter study to assess safety and efficacy of fexagratinib in patients with relapsed/refractory FGFR fusion-positive glioma.

Background: Oncogenic FGFR-TACC fusions are present in 3-5% of high-grade gliomas (HGGs). Fexagratinib (AZD4547) is an oral FGFR1-3 inhibitor with preclinical activity in FGFR-TACC+ gliomas. We tested its safety and efficacy in patients with recurrent FGFR-TACC + HGGs. Patients and Methods: TARGET (NCT02824133) is a phase I/II open-label multicenter study that included adult patients with FGFR-TACC + HGGs relapsing after ≥1 line of standard chemoradiation. Patients received fexagratinib 80 mg bd on a continuous schedule until disease progression or unacceptable toxicity. The primary endpoint was the 6-month progression-free survival rate (PFS6). Results: Twelve patients with recurrent IDH wildtype FGFR-TACC + HGGs (all FGFR3-TACC3+) were included in the efficacy cohort (male/female ratio = 1.4, median age = 61.5 years). Most patients (67%) were included at the first relapse. The PFS6 was 25% (95% confidence interval 5-57%), with a median PFS of 1.4 months. All patients without progression at 6 months (n = 3) were treated at first recurrence (versus 56% of those in progression) and remained progression-free for 14-23 months. The best response was RANO partial response in 1 patient (8%), stable disease in 5 (42%), and progressive disease in 6 (50%). Median survival was 17.5 months from inclusion. Grade 3 toxicities included lymphopenia, hyperglycaemia, stomatitis, nail changes, and alanine aminotransferase increase (n = 1 each). No grade 4-5 toxicities were seen. A 32-gene signature was associated with the benefit of FGFR inhibition in FGFR3-TACC3 + HGGs. Conclusions: Fexagratinib exhibited acceptable toxicity but limited efficacy in recurrent FGFR3-TACC3 + HGGs. Patients treated at first recurrence appeared more likely to benefit, yet additional evidence is required.

Intravenous Immunoglobulins for Bilateral Retinochoroiditis in Rhinovirus Infection: A Case Report.

A 43-year-old woman presented bilateral anterior granulomatous uveitis associated with bilateral disc edema and bilateral peripheral retinochoroidal lesions. Intravenous corticosteroids after negative investigations for infectious causes did not prevent spreading of the lesions and retinal atrophy. A diagnostic vitrectomy with vitreous analysis, including pan-genomic, next-generation sequencing showed a positive result for rhinovirus HRV B91, and the cytological analysis was suggestive of infection. Intravenous immunoglobulins associated with pegylated interferon-alpha strongly slowed the progression of the lesions and led to scarred and atrophic aspect in both eyes after 6 months. [Ophthalmic Surg Lasers Imaging Retina 2023;54:720-722.].

Efficacy and safety of Aflibercept for the treatment of inflammatory choroidal neovascularization: The ALINEA study.

PURPOSE: To evaluate mean change in best-corrected visual acuity (BCVA) at 52 weeks in patients with inflammatory choroidal neovascularization (CNV) treated with aflibercept. METHODS: We conducted a prospective non-comparative open-label trial. Following one mandatory intravitreal injection of aflibercept, patients were treated under a pro re nata (PRN) dosing regimen with monthly visits. RESULTS: A total of 19 patients were included, but one presented exclusion criteria; 16 patients were followed for the whole 52-week study, and data for the primary endpoint analysis were available for 14. At baseline, mean BCVA and mean central retinal thickness (CRT) were 64.53 (±19.64) letters and 351.79 (±97.77) µm, respectively. At 52 weeks, the mean change in BCVA was +9.50 (±12.90) letters [95%CI = +2.05-+16.95]. One patient had lost more than 15-letters at 24 weeks, and another one at 52 weeks. CRT change was -62.77 (±100.73) µm at 24 weeks and -66.53 (±97.47) µm at 52 weeks. There was a mean number of 3.56 (±3.29) intravitreal injections at 52 weeks (min = 1; max = 12). No serious ocular adverse events related to the treatment were reported. CONCLUSIONS: Our study shows that aflibercept is clinically effective, both anatomically and functionally in the treatment of inflammatory CNV. Following the first injection, the PRN strategy appears sufficient for treating most choroidal neovessels.

Precise, simplified diagnostic criteria and optimised management of initial-onset Vogt-Koyanagi-Harada disease: an updated review.

Vogt-Koyanagi-Harada (VKH) disease is a primary autoimmune stromal choroiditis. This review aimed to provide a novel perspective of the disease. We took into account recent developments in the understanding of the disease and crucial progress in investigational modalities of the choroid, which has led to new, simpler diagnostic criteria. We analysed recent novel notions in the literature and new diagnostic tools for VKH. We identified the following updates for VKH disease: (1) A crucial differentiation between the acute initial-onset and the chronic forms of the disease; (2) the integration of new, precise imaging methods to assess choroidal inflammation; (3) the promotion of simplified, more reliable diagnostic criteria for acute initial-onset of the disease, based on the sine qua non presence of diffuse choroiditis, detected with indocyanine green angiography (ICGA) and/or Enhanced Depth Imaging OCT (EDI-OCT); and (4) treatment optimisation through early, vigorous, sustained corticosteroid and nonsteroidal immunosuppression, as the first line of treatment for initial-onset VKH disease, and monitoring subclinical choroidal inflammation during follow-ups. Several studies have shown that most patients could discontinue treatment without an inflammation relapse. ICGA and EDI-OCT represented the methods of choice for precisely monitoring disease evolution. Simplified, precise, new diagnostic criteria allow early diagnosis of VKH. In VKH disease, inflammation exclusively originates in the choroidal stroma. Therefore, in many cases, early, sustained treatment, with dual corticosteroid and nonsteroidal immunosuppressive therapy can result in full "healing", which obviates chronic, uncontrolled, subclinical choroidal inflammation.

Anterior chamber tap cytology in acute postoperative endophthalmitis: a case-control study.

AIMS: To determine anterior chamber tap cytology characteristics in acute postoperative bacterial endophthalmitis. METHODS: 488 eyes of 488 patients were included in this retrospective case-control study. The study group included 93 eyes with bacteriologically documented endophthalmitis and 85 eyes with clinical endophthalmitis. The control group included 33 eyes with non-infectious postoperative inflammation, 116 eyes with acute uveitis and 161 cataract surgery eyes with no ocular inflammation. Cytological analysis, direct examination and microbiological cultures were performed in aqueous humour (AqH) samples. Inclusion criteria for the study group were the following: suspected endophthalmitis within 30 days following cataract surgery by phacoemulsification, secondary lens implantation, pars plana vitrectomy or intravitreal injection; best-corrected visual acuity (BCVA) <20/400; hypopyon or cyclitic membrane; absence of visibility of the retina; vitritis at a slit-lamp examination or in ultrasound B-scan. RESULTS: Cell line counts (mainly polymorphonuclear neutrophils) were significantly higher in the two endophthalmitis study subgroups than in the three control subgroups. The study group showed a predominance of polymorphonuclear neutrophils as opposed to the three control subgroups including uveitis (p<0.00001). The best sensitivity/specificity was obtained using a polymorphonuclear neutrophil threshold of 10 per field (sensitivity, 0.90; specificity, 0.75). The sensitivity of the bacterial culture was 32% in the AqH. High neutrophil count was associated with poorer initial BCVA (rs=0.62; p<0.00001) and higher risk of retinal detachment during (p=0.04) and after (p<0.001) hospitalisation. CONCLUSION: Anterior chamber tap cytology is a quick and accessible tool complementary to culture and PCR for the management of acute postoperative endophthalmitis.

Ciclosporin A in bilateral auto-immune chronic posterior uveitis associated with macular oedema: a Long-term Observational Safety and Efficacy Study.

OBJECTIVE: A non-interventional, longitudinal, retrospective follow-up study to assess CsA-induced nephrotoxicity (IN) and its reversibility after withdrawal in patients exhibiting a bilateral chronic posterior uveitis (CPU) associated with cystoid macular oedema (CMO) in at least one eye. Data from medical records between 1986 and 2013. METHODS: Primary outcome was the renal tolerance during and after CsA treatment assessed by plasma creatinine concentration and glomerular filtration rate (GFR) estimated by Chronic Kidney Disease Epidemiology (CKD-Epi) formula. Secondary outcomes were CsA through concentration, occurrence of cancers and ophthalmologic efficacy assessed by three parameters including CMO, vitreous inflammation, and best-corrected visual acuity BVCA changes. RESULTS: One hundred forty-three patients were followed for renal tolerance. Underlying diseases were Birdshot retinochoroiditis (n = 67), Behçet disease (n = 9), probable sarcoidosis (n = 23), sympathetic ophthalmia (n = 3), idiopathic (n = 41). After CsA discontinuation in 115 patients (mean treatment duration of 5.9 ± 3.8 years) mean plasma creatinine concentration was 82.2 ± 14.2 µmol/L versus 82.1 ± 14.1 µmol/L at baseline, mean GFR was 79.4 ± 13.9 mL/min versus 82.5 ± 14.3 mL/min at baseline, with no significant difference (respectively p = 0.91 and p = 0.09). Blood pressure did not significantly change during follow-up. CMO was completely resorbed in at least one eye, in 70.8% patients (n = 72) at 6 months, in 71.4% patients (n = 49) at 10 years and in 54.2% patients (n = 24) at 20 years. BCVA did not statistically change over time. CONCLUSION: Early and long-term monitoring of renal tolerance and dual adjustment of CsA doses in inflammatory stages of CPU were associated with reversible CsA IN. CsA could be effective in the treatment of CMO in CPU patients.

Hemodilution therapy using automated erythrocytapheresis in central retinal vein occlusion: results of a multicenter randomized controlled study.

BACKGROUND: Central retinal vein occlusion (CRVO) leads to poor visual outcome in most eyes. Abnormal hemorheology was suspected to play a major role in its pathogenesis. CRVO treatment is still a matter of debate but several studies have pointed out the efficacy of isovolumic hemodilution. The aim of this study was to assess the feasibility and efficacy of hemodilution using automated erythrocytapheresis in recent-onset CRVO. METHODS: In this prospective randomized controlled multicenter study, 61 consecutive CRVO patients were enrolled when they met the following criteria: CRVO lasting for 3 weeks or less, visual acuity ranging from 20/200 to 20/32, age between 18 and 85 years, no diabetes, no uncontrolled systemic hypertension, no antiplatelet or anticoagulant therapy, hematocrit higher than 38%, and signed informed consent. Patients were randomly assigned to the hemodilution group (n = 31) or to the control group (n = 30). Hemodilution therapy consisted of one session of erythrocytapheresis on outpatient basis, followed by additional session(s) for 6 weeks if needed. Target hematocrit was 35%. Follow-up was 12 months. RESULTS: No statistical differences in age, associated risk factors, or CRVO characteristics were observed at baseline between both groups. Mean visual acuity was equivalent to 20/80 in the hemodilution group and to 20/63 in the control group (non-significant difference). In the treated group, mean number of hemodilution sessions was 3.3 (range, 1 to 6), and no major side-effects occurred. At the 12-month follow-up visit, 64.5% of the hemodilution group had visual acuity of 20/40 or better compared to 40% of the control group (p = .048). Visual change was a gain of 1.7 ETDRS line in the hemodilution group versus a loss of 2.3 lines in the control group (p = .007). There was less conversion into an ischemic form in the hemodilution group (11%) than in the control group (50%, p = .004). Mean final retinal thickness was 289 µm in the hemodilution group versus 401 µm in the control group (p = .068). CONCLUSIONS: This multicenter controlled randomized study demonstrated that automated erythrocytapheresis is a safe and effective tool for performing hemodilution and confirmed that hemodilution therapy can improve the final prognosis of CRVO when applied in the early phase of the disease.

HLA-A29 Birdshot Retinochoroiditis in Its 5th Decade: Selected Glimpses into the Intellectual Meanderings and Progresses in the Knowledge of a Long-Time Misunderstood Disease.

The appraisal of HLA-A29 birdshot retinochoroiditis (BRC) was fraught with pitfalls and misunderstandings. Progress in investigational methods has led to better knowledge and management of the disease. Our aim was to assess some of the steps that have led to better characterisation of the clinical entity of BRC. We performed a literature search analysing the relevant progress in disease origin, investigational and imaging methods, clinicopathology and classification, diagnostic criteria and management. Following developments were judged essential in the better appraisal and understanding of the disease: (1) new immunopathological hypotheses regarding the role of endoplasmic reticulum peptidases, (2) the essential importance of HLA testing, (3) relevant imaging modalities among which indocyanine green angiography is crucial, (4) diagnostic criteria that allow early diagnosis and (5) need of an early prolonged, as well as aggressive treatment combining more than one immunosuppressive agent. Based on these findings it is now possible to better define BRC, an indolent however severe disease, unlike thought before, involving the choroidal stroma and the retina independently and concomitantly that can be diagnosed early thanks to indocyanine green angiography and should be treated early and relentlessly.