Photocoagulation or sham laser in addition to conventional anti-VEGF therapy in macular edema associated with TelCaps due to diabetic macular edema or retinal vein occlusion (TalaDME): a study protocol for a multicentric, French, two-group, non-commercial, active-control, observer-masked, non-inferiority, randomized controlled clinical trial.

BACKGROUND: Macular edema (ME) results from hyperpermeability of retinal vessels, leading to chronic extravasation of plasma components into the retina and hence potentially severe visual acuity loss. Current standard of care consists in using intravitreal injections (IVI), which results in a significant medical and economic burden. During diabetic retinopathy (DR) or retinal vein occlusion (RVO), it has recently been shown that focal vascular anomalies (capillary macro-aneurysms, also termed TelCaps) for telangiectatic capillaries may play a central role in the onset, early recurrence, and/or persistence of ME. Since targeted photocoagulation of TelCaps may improve vision, identification, and photocoagulation of TelCaps, it may represent a way to improve management of ME. OBJECTIVE: The Targeted Laser in (Diabetic) Macular Edema (TalaDME) study aims to evaluate whether ICG-guided targeted laser (IGTL), in association with standard of care by IVI, allows reducing the number of injections during the first year of treatment compared with IVI only, while remaining non-inferior for visual acuity. METHODS: TalaDME is a French, multicentric, two-arms, randomized, sham laser-controlled, double-masked trial evaluating the effect of photocoagulation of TelCaps combined to IVI in patients with ME associated with TelCaps. Patients with vision loss related to center involved ME secondary to RVO or DR and presenting TelCaps are eligible. Two hundred and seventy eyes of 270 patients are randomized in a 1:1 ratio to standard care, i.e., IVI of anti-VEGF solely (control group) or combined with IGTL therapy (experimental group). Stratification is done on the cause of ME (i.e., RVO versus diabetes). Anti-VEGF IVI are administered to both groups monthly for 3 months (loading dose) and then with a pro re nata regimen with a monthly follow-up for 12 months. The primary endpoint will be the number of IVI and the change in visual acuity from baseline to 12 months. Secondary endpoints will be the changes in central macular thickness, impact on quality of life, cost of treatment, and incremental cost-utility ratio in each groups. KEY SAFETY: Rare but severe AE linked to the use of IVI and laser, and previously described, are expected. In the sham group, rescue laser photocoagulation may be administered by the unmasked investigator if deemed necessary at month 3. DISCUSSION: The best management of ME associated with TelCaps is debated, and there have been no randomized study designed to answer this question. Given the fact that TelCaps may affect 30 to 60% of patients with chronic ME due to DR or RVO, a large number of patients could benefit from a specific management of TelCaps. TalaDME aims to establish the clinical and medico-economic benefits of additional targeted laser. The results of TalaDME may raise new recommendations for managing ME and impact healthcare costs. TRIAL REGISTRATION: EudraCT: 2018-A00800-55/ NCT03751501. Registration date: Nov. 23, 2018.

Revisiting the Use of Deep Temporalis Fascia Grafts in Ophthalmology.

PURPOSE: To report new indications for deep temporalis fascia (DTF) grafts in the ophthalmic field. METHODS: Monocentric retrospective interventional case series study. All the patients who underwent a DTF graft in an unpublished new indication over the study period (May 2020-October 2023) were included. For each patient, gender, age, graft indication, outcomes, complications, and follow-up duration were collected. In most cases, the DTF graft was covered by a vascularized flap. RESULTS: Eight patients underwent a DTF graft over the study period. The indications were: radiotherapy-induced scleral necrosis in three cases, tendinoplasty to replace the inferior rectus muscle tendon invaded by a locally advanced conjunctival carcinoma in one case, Ahmed glaucoma valve tube exposure in one case, intraocular lens with scleral fixation exposure in one case, orbital cerebrospinal fluid fistula (orbitorrhea) in one case, and post-traumatic complete corneal graft loss in one case. The DTF graft was successful in 87.5% of cases after a mean follow-up of 11.4 months. No complications were observed. CONCLUSIONS: DTF graft is a highly versatile graft that can be easily harvested. New indications for DTF grafts may include the repair of radiotherapy-induced scleral necrosis, the creation of oculomotor tendon and the temporary packing of large ocular tissue loss in an emergency context. Further studies with a longer follow-up are needed to confirm our preliminary results.

Roth spots in a Rendu-Osler-Weber syndrome.

PURPOSE: To describe the molecular diagnosis and atypical ocular presentation of a patient who suffered for a Rendu-Osler-Weber syndrome associated with juvenile polyposis (JP) syndrome. METHODS: This is a case report of a patient that underwent fundus examen, brain Magnetic Resonance Imaging (MRI) and arteriography. Genetic testing was performed by next-generation-sequencing (NGS). RESULTS: A 35-year-old woman presented with right hemiplegia with right homonymous lateral hemianopia and homolateral complete sensory deficit. She also had Roth spots in her left fundus. Genetic testing revealed a pathogenic variation in the heterozygous state in the SMAD-4 gene (c.1245_1248del). CONCLUSION: Hereditary Hemorrhagic Telangiectasia (HTT) also known as Rendu-Osler-Weber syndrome is a rare autosomal dominant disease which reveals mostly with epistaxis and cutaneous telangiectasias. Our clinical case reports Roth spots in the context of HTT associated with juvenile polyposis syndrome. SMAD-4 mutation may explain the presence of a carotid-ophthalmic aneurysm which is not a lesion usually found in HTT.

Surgery, Tissue Plasminogen Activator, Antiangiogenic Agents, and Age-Related Macular Degeneration Study: A Randomized Controlled Trial for Submacular Hemorrhage Secondary to Age-Related Macular Degeneration.

PURPOSE: To compare the efficacy and the safety of submacular hemorrhage (SMH) management using either surgical pars plana vitrectomy (PPV) or pneumatic displacement (PD) with tissue plasminogen activator (tPA) and vascular endothelial growth factor (VEGF) inhibitor added to each arm. DESIGN: Randomized, open-label, multicenter superiority study. PARTICIPANTS: Ninety patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older with recent SMH (≤ 14 days) of more than 2 optic disc areas and predominantly overlying the retinal pigment epithelium. METHODS: Patients were assigned randomly to surgery (PPV, subretinal tPA [maximum, 0.5 ml/50 µg], and 20% sulfur hexafluoride [SF6] tamponade) or PD (0.05 ml intravitreal tPA [50 µg] and 0.3 ml intravitreal pure SF6). Both groups were asked to maintain a head upright position with the face forward at 45° for 3 days after intervention and received 0.5 mg intravitreal ranibizumab at the end of the intervention, at months 1 and 2, as the loading phase, and then on a pro re nata regimen during a 6-month follow-up. MAIN OUTCOME MEASURES: The primary efficacy endpoint was mean best-corrected visual acuity (VA) change at month 3. The secondary endpoints were mean VA change at month 6, 25-item National Eye Institute Visual Function Questionnaire composite score value at months 3 and 6, number of anti-VEGF injections, and complications during the 6-month follow-up. RESULTS: Of the 90 patients randomized, 78 patients (86.7%) completed the 3-month efficacy endpoint visit. The mean VA change from baseline to month 3 in the surgery group (+16.8 letters [95% confidence interval (CI), 8.7-24.9 letters]) was not significantly superior to that in the PD group (+16.4 letters [95% CI, 7.1-25.7 letters]; adjusted difference ß, 1.9 [-11.0; 14.9]; P = 0.767). Both groups achieved similar secondary outcomes at month 6. No unexpected ocular safety concerns were observed in either group. CONCLUSIONS: Surgery did not yield superior visual gain nor additional benefit for SMH secondary to nAMD compared with PD at 3 months, with intravitreal anti-VEGF added to each arm. Both treatment strategies lead to a clinical improvement of VA without safety concerns for SMH over 6 months. Both design and results of the trial cannot be used to establish equivalence between treatments. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Identifying predictive factors for long-term visual recovery after corneal endothelial keratoplasty in Fuchs' dystrophy: Potential interaction between the corneal dysfunction and retinal status.

Introduction: Descemet membrane endothelial keratoplasty (DMEK) is the main treatment for Fuchs' dystrophy (FECD). The outcomes are excellent, but the final visual recovery may vary from patient to patient with sometimes no obvious reason of such a spread. Methods: We conducted a clinical prospective multicentric study to identify the predictive factors for the visual result 1 year after surgery. Eighty three patients (83 eyes) were included. Results: Postoperative BCVA after 1 year was 0.20 ± 0.18 logMAR. Logistic regression revealed that good visual recovery correlated negatively with preoperative central macular thickness (p < 0.001) and the need for rebubbling (p = 0.05), and positively with preoperative visual acuity (p = 0.009). Multivariate formula to predict the 1-year BCVA has been suggested. Discussion: Preoperative retinal status seems to be the main predictive factor for long-term visual result after DMEK. Our predictive multivariate model could assist in better informing the patient about the prognosis of the surgery, and in adjusting the therapeutic strategy also, further highlighting the essential collaboration between both cornea and retina subspecialists.

Real-Time (iOCT) Guided Epiretinal Membrane Surgery Using a Novel Forceps with Laser-Ablated Microstructure Tip Surface.

PURPOSE: We investigated intraoperative OCT (iOCT)-guided epiretinal membrane (ERM) and internal limiting membrane (ILM) removal using a novel forceps with a laser-ablated tip surface; it was designed to help prevent indentation force, shear stress, or tractional trauma when grasping very fine membranes. PATIENTS AND METHODS: This retrospective study included patients who underwent 23- and 25-gauge pars plana vitrectomy (PPV) for vitreoretinal interface disorders. ERM and ILM peeling was performed under guidance with microscope-integrated iOCT using novel ILM forceps with laser-ablated tip surfaces. These forceps were engineered to enhance friction when grasping tissue. Evaluation of ERM/ILM manipulation included postoperative slow-motion video analysis of the number of grasping attempts, initial ILM mobilization, and observed damage to retinal tissue. RESULTS: ERM/ILM removal was successfully performed in all patients, with an average of four grasp actions to initial membrane mobilization (91%). Additional use of a diamond-dusted membrane scraper was used in two cases (9%). Mean best-recorded visual acuity (BRVA) logMAR improved from 0.5 ± 0.34 to 0.33 ± 0.36 (p = 0.05) and mean central retinal thickness (CRT) improved from 462 ± 146 µm to 359 ± 78 µm (p = 0.002). Postoperative iOCT video analysis demonstrated hyper-reflectivity of the inner retinal layers associated with retinal hemorrhage in five eyes (22%), but no grasping-related retinal breaks. CONCLUSIONS: The texturized surface on the tips of the ILM forceps were found to be helpful for mobilizing ILM edges from the retinal surface. iOCT-guided ERM surgery also allowed for improved intraoperative tissue visualization. We believe that these two technologies helped reduce both unnecessary surgical maneuvers and retinal damage.

Comparative Evaluation of Two SD-OCT Macular Parameters (GCC, GCL) and RNFL in Chiasmal Compression.

Purpose: To evaluate the relationship between different macular thickness parameters analyzed by SD-OCT and the central visual field (VF) evaluated with automated kinetic perimetry in a cohort of patients with pituitary tumors. Methods: Data from patients with pituitary adenoma treated at Reims University Hospital between October 1st, 2017, and May 31st, 2018 were collected. All patients underwent an automated kinetic perimetry and a SD-OCT to map the ganglion cell complex (GCC), the ganglion cell layer (GCL) thickness and the retinal nerve fiber layer (RNFL) using devices from two different manufacturers. Univariate and multivariate analysis were used to evaluate the correlation between the area of central VF in square degrees (deg2) and the SD-OCT parameters (µm). Results: Eighty-eight eyes were included in the analysis. All the thickness parameters measured in SD-OCT decreased with the visual field alteration. The best correlation was observed between superior thickness parameters (GCC, GCL) and the inferior central visual field. The most pertinent predictive factors for visual field loss were the inferior central GCL and the nasal RNFL (both AUC=0.775) with a sensitivity respectively of 86% and 70%. Conclusion: This study suggests that both GCC, GCL thickness parameters could be reliable predictors of central visual field impairment in patients with pituitary tumors. There was no significative difference between both devices.

Severe Primary Open-Angle Glaucoma and Agricultural Profession: A Retrospective Cohort Study.

While exposure to pesticides is a known risk factor for neurodegenerative brain diseases, little is known about the influence of environment on glaucoma neuropathy. We aimed to determine whether farmers are at higher risk of developing severe primary open-angle glaucoma (POAG). This retrospective cohort study (tertiary referral center, Reims University Hospital, France) included patients diagnosed with POAG in the last two years. Univariate analysis and adjusted multivariate logistic regression were performed to evaluate the association between agricultural profession and all recorded data. Glaucoma severity (primary outcome) and the number of patients who underwent filtering surgery (secondary outcome) were analyzed. In total, 2065 records were screened, and 772 patients were included (66 in the farmer group and 706 in the nonfarmer group). The risk of severe glaucoma was higher in the farmer group (adjusted odds ratio (aOR) 1.87, p = 0.03). More patients underwent filtering surgery in the farmer group in univariate analysis (p = 0.02) but with no statistical significance after adjustment (p = 0.08). These results suggest pesticide exposure may be a factor accelerating the neurodegeneration in POAG, although a direct link between the agricultural profession and the disease requires further extended studies to be demonstrated.

Corneal in vivo confocal microscopy to detect belantamab mafodotin-induced ocular toxicity early and adjust the dose accordingly: a case report.

BACKGROUND: New targeted antibody-drug conjugates (ADCs) against multiple myeloma are known to induce adverse effects that may lead to treatment discontinuation. Preclinical studies reported early severe ocular damage related to the use of belantamab mafodotin (belamaf), including ocular surface inflammation, severe dry eye, and a specific toxicity to the cornea, namely microcystic keratopathy. While belamaf-induced ocular changes have not been prospectively studied, a better understanding of mechanisms involved as well as kinetics may aid in anticipating dose adjustment rather than stopping the treatment once clinical ocular damage is too severe. CASE PRESENTATION: A 61-year-old woman scheduled for belamaf as a fifth-line treatment against multiple myeloma was prospectively included. Clinical examinations were performed before and every 3 weeks afterward, together with in vivo confocal microscopy (IVCM) of the cornea. Visual acuity, symptoms, slit-lamp examination, and ultrastructural changes of the cornea were recorded according to the received dose of belamaf. More precisely, kinetics, shape, density, and location of the toxic corneal lesions have been followed and analyzed using IVCM. Also, specific lesions at the sub-basal nerve plexus layer were detected and characterized for the first time. This advanced approach allowed a better understanding of the belamaf-induced toxicity, further balancing the dose to maintain good vision and eye health while continuing the treatment. CONCLUSIONS: Systematic ultrastructural analysis and follow-up of the corneal state during ADCs treatment for multiple myeloma may open new avenues in the therapeutic approach. Early preclinical detection of ocular damage may accurately contribute to finding the correct dose for each patient and not stopping the treatment due to severe ocular adverse effects.

Functional and anatomical outcomes after successful repair of macula-off retinal detachment: a 12-month follow-up of the DOREFA study.

PURPOSE: To report visual and anatomical outcomes and determine predictors of good visual acuity (VA) recovery after macula-off rhegmatogenous retinal detachment (RD). METHODS: Prospective multicentre study including 115 eyes from 115 patients successfully operated on for RD, with assessment of VA and spectral-domain optical coherence tomography (SD-OCT) macular images at 1, 3, 6 and 12 months after surgery. RESULTS: Over the follow-up period, VA significantly improved from median [IQR] 62 [46; 72] ETDRS letters at 1 month to 75 [67; 80] ETDRS letters at 12 months (p < 0.001) with a concomitant decreased number of eyes with any SD-OCT lesions (p < 0.001). The presence of subretinal fluid (SRF) significantly decreased (p < 0.001), as did the number of photoreceptor (PR) layer lesions (p = 0.04). At 12 months, lesions in the PR layer and poor VA recovery were significantly associated with a longer time to surgery (p = 0.007 and p < 0.001, respectively). The rate of patients without PR lesions increased from 40.9% at 1 month to 60.0% at 6 months and 73.9% at 12 months (p < 0.001). The incidence of epiretinal membrane (ERM) significantly increased (p < 0.001), while cystoid macular oedema (CME) remained stable over time. Visual acuity (VA) at 3 months postoperatively was a good reflection of final VA recovery (p < 0.001). CONCLUSION: Visual acuity (VA) improved in parallel with the decreasing number of eyes with SD-OCT lesions after macula-off rhegmatogenous RD. A long time to surgery was the only preoperative factor associated with poor VA recovery after retinal detachment surgery.

Comparing Heads-Up versus Binocular Microscope Visualization Systems in Anterior and Posterior Segment Surgeries: A Retrospective Study.

BACKGROUND: Three-dimensional (3D) visualization systems, also known as heads-up systems, are now available for eye surgery and as with every new device there is need for a specific evaluation. OBJECTIVES: The aim of this study was to compare the efficiency, surgical comfort, and safety of a 3D visualization system to a standard binocular microscope (BM) in routine ophthalmologic procedures. METHOD: After a 4-week training period, a 3D visualization system (Ngenuity, Alcon®) available in one of the Robert Debré Hospital Ophthalmology Departments' operating rooms was compared to a standard BM (OPMI LUMIRA 700, Zeiss®), in the process of a call for new device evaluation. From December 2017 to March 2018, 5 surgeons and their respective residents were asked to fill in a questionnaire for all procedures. Before the surgery, the surgeon recorded: (i) the type of surgery (cataract [PK], retinal detachment [RD], epiretinal membrane peeling [ERM], macular hole, vitreous haemorrhage [VH]), (ii) the type of visualization system chosen (3D or BM), and (iii) the estimated surgical risk (low, intermediate, or high grade). At the end of the procedure, the primary surgeon recorded the remaining parameters, including: (i) surgery duration, (ii) intraoperative complications, (iii) percentage of endoillumination for posterior segment surgeries, (iv) status of the operator (senior or resident) and operator switch if necessary (senior only, resident only, or resident with help of the senior), and rated: (i) the visual comfort (low, normal, excellent), (ii) the operative fluency (low, normal, excellent), (iii) backaches (none, low, moderate, important), and (iv) headaches (range from 0 to 10). Age and sex were collected retrospectively. The procedures performed with 3D and BM were subsequently compared using univariate (χ2, Fisher, Wilcoxon) and multivariate analysis (generalized linear model), allowing us to identify parameters independently associated with PK surgery duration. RESULTS: A total of 102 valid questionnaires, relative to 73 PK and 29 vitreoretinal procedures, respectively, were analysed. As regards PK (3D, n = 25 vs. BM, n = 48), the mean age, sex ratio, surgical risk, intraoperative complications (1/25 vs. 4/48), visual comfort, backaches, and headaches were similar between the two systems. The use of 3D allowed faster PK surgeries (16.44 ± 4.36 vs. 21.44 ± 7.50 min; p = 0.007) and slightly enhanced the operative fluency. In vitreoretinal surgeries (3D, n = 14 vs. BM, n = 15), no obvious differences between the two visualization systems were observed, although the use of the 3D system was found to slightly decrease the operative fluency. Parameters independently associated with PK surgery duration were 3D visualization (ß = -4.4 ± 1.4; p = 0.002), high preoperative surgical risk (ß = 6.2 ± 2.4; p = 0.012), intraoperative complications (ß = 8.7 ± 2.6; p = 0.001), and surgeon status (ß = -4.4 ± 1.3; p = 0.001) in univariate and multivariate analysis. CONCLUSIONS: 3D visualization can be safely used in routine practice. It slightly improves the operative fluency, allowing faster PK surgery.

COMPARING INTRAVITREAL AIR AND GAS FOR THE TREATMENT OF VITREOMACULAR TRACTION.

PURPOSE: To compare the effect of intravitreal injections of air with gas on vitreomacular traction (VMT) release and attempt to analyze predictive factors for success. METHODS: The medical records of patients with symptomatic VMT undergoing intravitreal injections (0.3 mL) of either octafluoropropane (C3F8) or air were retrospectively reviewed. The VMT release (primary end point) and the best-corrected visual acuity (secondary end point) were noted 1 month after injection. At baseline and 1 month after the injection, a macular optical coherence tomography was performed. RESULTS: Twenty-four eyes of 22 patients were included. Vitreomacular traction was released in 10 cases, 7 among 11 C3F8-injected eyes (63%) and 3 among 13 air-injected eyes (23%) (P = 0.045). In eyes with released VMT, ETDRS improved from 61 ± 35 (0-100) to 65 ± 37 (0-100) 1 month after the injection (P = 0.03). All patients with VMT release had a horizontal vitreomacular adhesion of less than 600 µm. Five eyes (23%) underwent vitrectomy after the injection of gas or air. CONCLUSION: Posterior vitreous detachment in VMT can be observed with both air and gas injection with a low complication rate. The occurrence of VMT release observed with air seemed to be less frequent than that observed with gas.

CD160 Expression in Retinal Vessels Is Associated With Retinal Neovascular Diseases.

Purpose: Anti-angiogenic agents stand first in the treatment of neovascular diseases of the retina. CD160 appeared in several experimental studies as a marker of activated endothelial cells, suggesting it could represent a promising target for novel anti-angiogenic therapies. The aim of the present study was to assess the distribution of CD160 in the human eye, and to search for a possible correlation with retinal neovascular diseases. Methods: The physiological distribution of CD160 in the normal eye was assessed with immunolabeling in 10 human donor eyes. Then, in a retrospective cohort of 75 surgical retinal specimens, the density of CD160+ microvessels was evaluated, along with immunolabeling on serial sections against ERG (pan-endothelial cell marker), CD105 (activated endothelial cell marker), and α-SMA (pericyte cell marker). The cohort was divided into two groups: 29 patients with neovascular disease (NV+) and 46 control patients (NV-). Results: CD160 was physiologically expressed by several cell types: endothelial cells of retinal blood vessels, ganglion cells, macrophages, epithelial cells of the conjunctiva, ciliary body, and retinal pigment epithelium. In the patient cohort, the percentage of CD160+ vessels in the retina was significantly and independently higher in patients suffering from neovascular diseases (P = 0.04). On the contrary, the expression of CD105 was correlated neither with retinal neovascular diseases, nor with CD160 expression. Conclusions: CD160 was expressed in some retinal vessels in both normal and pathologic eyes. CD160 expression by endothelial cells of retinal vessels was correlated with ocular neovascular diseases. CD160 could therefore represent an interesting target for novel anti-angiogenic therapies.

A new autosomal dominant eye and lung syndrome linked to mutations in TIMP3 gene.

To revisit the autosomal dominant Sorsby fundus dystrophy (SFD) as a syndromic condition including late-onset pulmonary disease. We report clinical and imaging data of ten affected individuals from 2 unrelated families with SFD and carrying heterozygous TIMP3 mutations (c.572A > G, p.Y191C, exon 5, in family 1 and c.113C > G, p.S38C, exon 1, in family 2). In family 1, all SFD patients older than 50 (two generations) had also a severe emphysema, despite no history of smoking or asthma. In the preceding generation, the mother died of pulmonary emphysema and she was blind after the age of 50. Her two great-grandsons (<20 years), had abnormal Bruch Membrane thickness, a sign of eye disease. In family 2, eye and lung diseases were also associated in two generations, both occurred later, and lung disease was moderate (bronchiectasis). This is the first report of a syndromic SFD in line with the mouse model uncovering the role of TIMP3 in human lung morphogenesis and functions. The TIMP3 gene should be screened in familial pulmonary diseases with bronchiectasis, associated with a medical history of visual loss. In addition, SFD patients should be advised to avoid tobacco consumption, to practice sports, and to undergo regular pulmonary examinations.

Clinical Characteristics and Risk Factors of Extensive Macular Atrophy with Pseudodrusen: The EMAP Case-Control National Clinical Trial.

PURPOSE: To assess the association of clinical and biological factors with extensive macular atrophy with pseudodrusen (EMAP) characterized by bilateral macular atrophy occurring in patients aged 50 to 60 years and a rapid progression to legal blindness within 5 to 10 years. DESIGN: A national matched case-control study. PARTICIPANTS: Participants were recruited in 10 French Departments of Ophthalmology and their associated clinical investigation centers. All 115 patients with EMAP had symptoms before the age of 55 years due to bilateral extensive macular atrophy with a larger vertical axis and diffuse pseudodrusen. Three controls without age-related macular degeneration (AMD) or retinal disease at fundus examination were matched for each patient with EMAP by gender, age, and geographic area (in total 415). METHODS: Subjects and controls underwent an eye examination including color, red-free autofluorescent fundus photographs and spectral-domain optical coherence tomography with macular analysis. The interviews collected demographic, lifestyle, family and personal medical history, medications, and biological data. Associations of risk factors were estimated using conditional logistic regression. MAIN OUTCOME MEASURES: Extensive macular atrophy with pseudodrusen status (cases vs. controls). RESULTS: Extensive macular atrophy with pseudodrusen most frequently affected women (70 women, 45 men). After multivariate adjustment, family history of glaucoma or AMD was strongly associated with EMAP (odds ratio [OR], 2.3, P = 0.008 and OR, 1.5, P = 0.01, respectively). No association was found with cardiac diseases or their risk factors. Mild and moderate kidney disease and higher neutrophil rate were associated with a reduced risk of EMAP (OR, 0.58, P = 0.04; OR, 0.34, P = 0.01; and OR, 0.59, P = 0.003, respectively). On the contrary, eosinophilia (OR, 1.6; P = 0.0002), lymphocytosis (OR, 1.84; P = 0.0002), increased erythrocyte sedimentation rate (OR, 6.5; P = 0.0005), decreased CH50 (P = 0.001), and high plasma C3 level (P = 0.023) were significantly associated with a higher risk of EMAP. CONCLUSIONS: This study documents an association between EMAP and family history of AMD and glaucoma, a clear female predominance, and a systemic inflammatory profile. The reduced CH50 and increased C3 plasma values could reflect a more severe complement pathway dysfunction than in AMD, leading to early pseudodrusen and rapid development of geographic atrophy. There is no association of EMAP with AMD cardiac diseases or cardiac risks, including cigarette smoking.

Cytopathology of Vitreous Humor Samples in Routine Practice.

OBJECTIVE: To describe findings in vitreous fluid samples in routine cytology practice. STUDY DESIGN: The pathology archives from 1988 to 2008 at our institution were searched for vitreous samples. The slides were reviewed and clinical and follow-up information was obtained. RESULTS: One hundred and eighty-two vitreous fluid samples from 166 patients were analyzed. Most of the samples had been collected for vitreous hemorrhage (75 cases). The second reason for vitreous sample cytological evaluation was an intraocular inflammatory process (55 cases). A specific cause of inflammation was found by combining clinical, microbiological and cytopathological findings in 19 cases, i.e. infection in 7, sarcoidosis in 3, retinal necrosis in 3, lens-induced endophthalmitis in 2, uveitis associated with systemic disease in 2, retrobulbar neuritis in 1 and sympathetic ophthalmia in 1. Among the 19 samples from 16 patients collected to rule out malignancy, 8 had a confirmed intraocular malignancy. Malignant cells were observed in 5 cases (3 lymphomas, 1 melanoma and 1 carcinoma). Undiagnosed malignancies included 2 lymphomas and 1 choroidal melanoma. Other samples were collected during surgery for retinal detachment and cataracts. CONCLUSIONS: In routine practice, cytology of the vitreous fluid is performed in many and varied situations that are most often nonneoplastic. In nonneoplastic cases, cytology is a useful adjunct to vitrectomy, in spite of its limitations.

Prognostic value of retinal nerve fiber layer thickness for postoperative peripheral visual field recovery in optic chiasm compression.

UNLABELLED: OBJECT.: The authors' objective was to evaluate the predictive value of preoperative axonal loss for peripheral visual field recovery after surgery for optic chiasm compression. METHODS: Consecutive patients with optic chiasm compression in the period from October 2010 through August 2012 were retrospectively studied. Time-domain optical coherence tomography (OCT) had been performed before surgery. Kinetic automated perimetry had been performed before and after surgical decompression. The area of the peripheral isopter (square degrees [deg(2)]) was assessed. Postoperative improvement was defined as an increase of 25 deg(2) or more. RESULTS: Sixty-eight eyes in 34 patients were included in the analysis. In 44 eyes the visual field improved after surgery, and in 24 eyes it was unchanged or worse. Nasal retinal nerve fiber layer (RNFL) thickness was a good prognostic factor for peripheral visual field recovery (OR 1.56 per 15 µm, p = 0.041). CONCLUSIONS: Peripheral visual field recovery after surgery for optic chiasm compression is predicted by nasal RNFL thickness, which is in accordance with the retinotopy of retinal ganglion cells, as nasal axons decussate at the optic chiasm.

Electrophysiological retinal pigment epithelium changes observed with indocyanine green, trypan blue and triamcinolone.

BACKGROUND: Intravitreal application of indocyanine green (ICG), trypan blue (TB) or triamcinolone (TA) during vitreoretinal surgery has been associated with severe damage to the retinal pigment epithelium (RPE). However, the physiological background of these findings remains to be assessed. METHODS: In bovine RPE choroid preparations maintained in Ussing chambers, the effect of apical application of ICG, TA (filtered and not filtered) and TB at different concentrations was evaluated. The electrophysiological parameters (transepithelial potential, tissular resistance and short-circuit current) were continuously monitored. The experiments were conducted either in daylight or in dark-adapted conditions. RESULTS: After apical application of ICG and TA (purified and not purified), all bioelectrical parameters were affected in a dose-dependent manner. No significant changes were observed when the preparations were exposed to daylight. No changes were observed with TB. CONCLUSIONS: The electrophysiological results of apical application may explain the toxic effects observed after intraoperative use of ICG and TA. In this RPE study, TB appears to be the safest visualization aid for vitreoretinal surgery.

The ocular anomalies in a cystinosis animal model mimic disease pathogenesis.

Cystinosis is a lysosomal storage disorder characterized by abnormal accumulation of cystine, which forms crystals at high concentrations. The causative gene CTNS encodes cystinosin, the lysosomal cystine transporter. The eye is one of the first organs affected (corneal lesions and photophobia in the first and visual impairment in the second decade of life). We characterized the ocular anomalies of Ctns-/- mice to determine whether they mimic those of patients. The most dramatic cystine accumulation was seen in the iris, ciliary body, and cornea of Ctns-/- mice. Consistently, Ctns-/- mice had a low intraocular pressure (IOP) and seemed mildly photophobic. Retinal cystine levels were elevated but increased less dramatically with age. Consistently, the retina was intact and electroretinogram (ERG) profiles were normal in mice younger than 19 mo; beyond this age, retinal crystals and lesions appeared. Finally, the lens contained the lowest cystine levels and crystals were not seen. The temporospatial pattern of cystine accumulation in Ctns-/- mice parallels that of patients and validates the mice as a model for the ocular anomalies of cystinosis. This work is a prerequisite step to the testing of novel ocular cystine-depleting therapies.

Quantification of metamorphopsia in patients with epiretinal membranes before and after surgery.

BACKGROUND: To evaluate quantification of metamorphopsia before and after the removal of unilateral epiretinal membrane (ERM). METHODS: One hundred and four consecutive patients with unilateral ERM scheduled for membrane peeling were prospectively enrolled. A complete ophthalmologic examination was performed. Metamorphopsia was evaluated, with standard Amsler grids and a laser grid generated with a scanning laser ophthalmoscope (SLO). The SLO procedure determined the area of distortion and was performed twice at a 30-minute interval to evaluate its reproducibility. The result was considered to be reliable when the area of distortion was identical in both SLO test sessions. One year after surgery, a complete ophthalmologic examination was performed. Metamorphopsia was again quantified with the SLO procedure. RESULTS: Before surgery, a reliable quantification of metamorphopsia (defined as area of distortion) could be performed in 98 patients (94%). Among these patients, 85 completed the follow-up of 12 months after surgery. Of these 85 patients, visual distortions had been detected preoperatively in 48 patients (56%). One year after surgery, visual distortions were detected in only 11 patients (13%). In 48 patients with preoperative distortions, the decrease of the area of distortion correlated with the change in visual acuity (r = -0.460, p = 0.011). CONCLUSIONS: SLO-based evaluation of metamorphopsia made it possible to provide a fast and reliable method for preoperative and post-operative quantification of visual distortion in patients undergoing ERM removal.