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 All the patients who underwent a DTF graft in an unpublished new indication over the study period (May 2020-October 2023) were included.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.

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.

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.

Increased intravitreal glucose in rhegmatogenous retinal detachment.

PURPOSE: Altered glucose metabolism, along with low-grade inflammation, has been proposed to be involved in retinal detachment (RD)-induced cone loss. Here, we assessed intravitreal glucose and cytological profile in patients with macula-off RD. METHODS: Glucose concentration was analysed in vitreous samples from 137 non-diabetic patients undergoing vitrectomy for either primary macula-off RD (n = 73) or epiretinal membrane (ERM; n = 64). Cellularity was assessed in vitreous cytospin preparations by a semi-quantitative immunostaining approach. RESULTS: Intravitreal glucose concentration was higher in the RD group (2.28 mmol.L-1 n =73 vs 1.6 mmol.L-1 n = 64; p < 0.0001). Overall cellularity and density of macrophages were significantly higher in the vitreous of RD patients (respectively p = 0.003 and p < 0.0001). Among the RD patients, intravitreal glucose concentration correlated with macrophages density (p = 0.002): its levels remained significantly higher in eyes in which macrophages were innumerable compared to lower macrophages densities RD eyes (p = 0.0095). CONCLUSIONS: We observed a strong relationship between intravitreal glucose concentration and vitreous macrophage density. Additional indicators for vitreous glycation and low-grade inflammation should be further studied.

Giant cell arteritis in the elderly / Maladie de Horton du sujet âgé

Introduction: Giant cell arteritis (GCA) or Horton's disease is a segmental and focal inflammation of large and medium-sized arteries mostly seen in patients of 50 years and older. There is also a peak frequency in individuals between the ages of 70 and 80. However, clinical data is scarce in this age group and especially in patients over 80. Methods: A retrospective study comprised of patients diagnosed with Horton's arteritis between 2012 and 2017, according to the American Society of Rheumatology, was conducted at Reims University Hospital. Patients were assigned to two groups according to age (≤ 75 and < 75) in order to evaluate and compare the impact of age on diagnosis, treatment and prognosis. Results: A total of 67 patients were studied. The mean age upon diagnosis was 75,85 ±8.5 years; 36 patients (53.7%) 75 years or younger and 31 patients older than 75. There was a female predominance (43 patients), 22 patients aged 75 years or younger and 21 older than 75. The mean follow up duration was 43.02 months in patients aged 75 years or younger and 30.99 in patients older than 75. This represents a difference of more than one year in terms of follow up, but is not statistically significant (p = 0.620). Eleven patients (16.4%) died during follow up: 5 patients (13.9%) aged 75 years or younger and 6 patients (19.4%) older than 75 (p = 0.547). Aortitis was significantly less seen in patients older than 75 (p = 0.0410). Conclusion: Our study showed no significant difference in either age group. However, aortitis was less seen in patients older than 75 years. Patients aged 75 or younger seemed more prone to relapses, but their follow up periods were shorter.

Introduction: L'artérite à cellules géantes (ACG) ou maladie de Horton est une artérite inflammatoire segmentaire et focale des artères de gros et moyen calibre du sujet de plus de 50 ans, avec un pic de fréquence chez le sujet très âgé entre 70 et 80 ans. Dans cette classe d'âge et au-delà de 80 ans, les données cliniques concernant l'AGC sont peu nombreuses. Notre objectif est de documenter ces dernières à travers une étude monocentrique menée sur une population avec une AGC avérée. Patients et méthode: Nous avons mené une étude rétrospective, monocentrique sur les dossiers médicaux de patients diagnostiqués artérite de Horton selon les critères de l'ASR entre 2012 et 2017 au CHU de Reims. Pour évaluer l'influence de l'âge sur le plan diagnostic, thérapeutique, du suivi et du pronostic, nous avons comparé des patients de 75 ans et moins (≤ 75 ans) à ceux de plus de 75 ans (> 75 ans) sur ces différents points. Résultats: Soixante-sept patients ont été inclus. L'âge moyen au diagnostic de ces patients était de 75,85 ± 8,5 ans ; 36 patients (53,7 %) étaient âgés de 75 ans ou moins (dont 22 femmes) et 31 patients (46,3 %) étaient âgés de plus de 75 ans (dont 21 femmes). La médiane de suivi était de 43,02 mois chez les patients ≤ 75 ans et de 30,99 mois chez les > 75 ans, soit près d'un an de différence, mais non significative (p = 0,620). Onze patients (16,4 %) étaient décédés au cours du suivi, 5 (13,9 %) chez les patients ≤ 75 ans et 6 (19,4 %) chez les patients de > 75 ans (p = 0,547). Les patients > 75 ans avaient significativement moins d'aortite (p = 0,0410). Il y avait une tendance à moins de rechute chez les patients de > 75 ans (p = 0,067). Pour les autres symptômes ou anomalies biologiques, les résultats de la biopsie d'artère temporale, la prise en charge thérapeutique, les complications iatrogènes et les décès, aucune différence significative n'était mise en évidence entre les deux groupes (p = ns). Conclusion: Notre étude montre peu de différence en ce qui concerne l'AGC entre les patients > 75 ans et ceux ≤ 75 ans. Toutefois, les patients > 75 ans ont moins d'aortite que les sujets plus jeunes. Il semble également y avoir une tendance à davantage de rechute chez les sujets les plus jeunes, sous réserve d'une durée de suivi plus courte d'un an, cliniquement pertinente, chez les sujets les plus âgés.

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.

Association Between the Tissue and Circulating Advanced Glycation End-Products and the Micro- and Macrovascular Complications in Type 1 Diabetes: The DIABAGE Study.

INTRODUCTION: Type 1 diabetes is associated with an increased risk of vascular complications. We aimed to investigate the association between serum and tissue advanced glycation end-products (AGEs) and micro- and macrovascular complications in type 1 diabetes (T1D). METHODS: We conducted a cross-sectional study on 196 adults with T1D (mean age 44.53 ± 16, mean duration of diabetes 22 ± 12 years, mean HbA1c 8 ± 1.2%). AGEs were measured in blood serum (i.e., carboxymethyllysine (CML), methylglyoxal-hydroimidazolone-1 (MGH1), and pentosidine) and by measurement of skin autofluorescence (SAF). Associations between AGEs levels and vascular complications were analyzed using binary logistic regression. Correlations between AGEs and pulse wave velocity (PWV) were also assessed by linear regressions. Significant differences were set for p values less than 0.05. RESULTS: We found positive associations between different AGEs and vascular complications. SAF was associated with both microangiopathy (retinopathy: OR = 1.92, p = 0.011; neuropathy: OR = 2.02, p = 0.04; any microangiopathy: OR = 2.83, p < 0.0001) and macroangiopathy (coronaropathy: OR = 3.11, p = 0.009; any macroangiopathy: OR = 2.78, p = 0.003). For circulating AGEs, pentosidine was significantly associated with coronaropathy (OR = 1.61, p = 0.01) and any macroangiopathy (OR = 1.52, p = 0.005) while MGH1 was associated with nephropathy (OR 1.72, p = 0.03). Furthermore, a significant linear correlation was found between PWV and SAF (r = 0.43, p < 0.001), pentosidine (r = 0.28, p < 0.001), and MGH1 (r = 0.16, p = 0.031), but not for CML (r = 0.03, p = 0.598). CONCLUSIONS: Skin autofluorescence appears to be a useful marker for investigating both micro- and macrovascular complications in T1D. In this study, pentosidine was associated with macroangiopathy and MGH1 with nephropathy among the circulating AGEs. Furthermore, the correlations between PWV and AGEs may suggest their value in early prediction of vascular complications in T1D.

First use of a new rapid multiplex PCR system for the microbiological diagnosis and the clinical management of severe infectious keratitis: A case report.

Purpose: We report the use of a rapid multiplex polymerase chain reaction (PCR) system in the microbiological diagnosis and the therapeutic management of a severe bacterial keratitis case. Observations: During the management of a severe bacterial keratitis case, standard microbiological diagnostic methods were performed. At the same time, an additional ocular swab sampling from the cornea was performed and analyzed using two rapid multiplex PCR assays allowing the simultaneous detection of 29 different virus, yeast and bacteria genomes. Using combination of two rapid multiplex PCR systems, the microbiological diagnosis of a severe Pseudomonas aeruginosa induced keratitis was performed within 90 minutes after an ocular sampling. A rapid subsequent adaptation of local antibiotic treatment was performed allowing to the young patient to regain 6 months after her hospital admission a final visual acuity of 20/20 in her right eye. Conclusions and importance: The present case report suggests that the use of a rapid multiplex PCR strategy may result in a decrease of the mean hospital stage duration for severe infectious keratitis and in an improvement of the clinical outcome of severe keratitis infections. Nevertheless, additional prospective studies are needed to evaluate whether this innovative strategy may replace the current standard approach and optimize the therapeutic management of severe corneal infections.

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.

New model to better diagnose dry eye disease integrating OCT corneal epithelial mapping.

PURPOSE: To optimise the objective diagnosis of dry eye disease (DED), the capabilities of wide corneal epithelial mapping using optical coherence tomography (OCT) were studied and subsequently integrated into a new scoring method. METHODS: Fifty-nine patients (118 eyes) with DED and 55 control subjects (110 eyes) were included. All patients underwent a complete ocular surface evaluation. Corneal epithelial thickness was collected using OCT for seven zones. DED and the control group were compared using a t-test, and univariate receiver operating characteristic (ROC) curves were calculated to define the diagnostic ability of OCT epithelial mapping. Multivariate analyses were performed using artificial intelligence (random forest) and logistic regression approaches to define the best way to integrate OCT mapping in the diagnosis of DED. Then, a final multivariable model for diagnosing DED was validated through a bootstrapping method. RESULTS: The DED group had significant epithelial thinning compared with the controls, regardless of location. Superior intermediate epithelial thickness was the best marker for diagnosing DED using OCT (binormal estimated area under ROC: 0.87; best cut-off value: 50 µm thickness). The difference between the inferior and superior peripheral zones was the best marker for grading the severity of DED (analysis of variance, p=0.009). A multivariate approach identified other significant covariables which were integrated into a multivariate model to improve the sensitivity (86.4%) and specificity (91.7%) of this innovative diagnostic method. CONCLUSION: Including OCT corneal epithelial mapping in a new diagnostic tool for DED could allow optimisation of the screening and staging of the disease in current practice as well as for clinical research purposes.

CRB1-Related Retinal Dystrophies in a Cohort of 50 Patients: A Reappraisal in the Light of Specific Müller Cell and Photoreceptor CRB1 Isoforms.

Pathogenic variants in CRB1 lead to diverse recessive retinal disorders from severe Leber congenital amaurosis to isolated macular dystrophy. Until recently, no clear phenotype-genotype correlation and no appropriate mouse models existed. Herein, we reappraise the phenotype-genotype correlation of 50 patients with regards to the recently identified CRB1 isoforms: a canonical long isoform A localized in Müller cells (12 exons) and a short isoform B predominant in photoreceptors (7 exons). Twenty-eight patients with early onset retinal dystrophy (EORD) consistently had a severe Müller impairment, with variable impact on the photoreceptors, regardless of isoform B expression. Among them, two patients expressing wild type isoform B carried one variant in exon 12, which specifically damaged intracellular protein interactions in Müller cells. Thirteen retinitis pigmentosa patients had mainly missense variants in laminin G-like domains and expressed at least 50% of isoform A. Eight patients with the c.498_506del variant had macular dystrophy. In one family homozygous for the c.1562C>T variant, the brother had EORD and the sister macular dystrophy. In contrast with the mouse model, these data highlight the key role of Müller cells in the severity of CRB1-related dystrophies in humans, which should be taken into consideration for future clinical trials.

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.

Characterization of SSBP1-related optic atrophy and foveopathy.

Dominant optic atrophy (DOA) is genetically heterogeneous and most commonly caused by mutations in OPA1. To distinguish between the classical OPA1-related and the recently identified SSBP1-related DOAs, the retina and fovea of 27 patients carrying the SSBP1 p.Arg38Gln variant were scrutinized using 20° × 20° macular cube and 30° and 55° field fundus autofluorescence photographs. Age of onset, visual acuity, retinal nerve fiber layer and macular thicknesses were recorded. Three SSBP1-patients were asymptomatic, 10 had isolated DOA, and 12 had a combined DOA plus foveopathy. The foveopathy, with a tiny defect of the ellipsoid and interdigitation lines, was similar in all patients, independent of age. There were no significant statistical differences in terms of visual acuity and SD-OCT measurements between patients with isolated DOA (mean visual acuity in decimals: 0.54 ± 0.41) and those with combined foveopathy (0.50 ± 0.23). Two patients over 50 years of age developed a progressive rod-cone dystrophy, leading to severe visual impairment. SSBP1-related DOA shares similarities with OPA1-related DOA with an incomplete penetrance and an early childhood visual impairment. Nevertheless, the presence of a congenital foveopathy with no impact on visual acuity is a major criterion to distinguish SSBP1 cases and orient the appropriate genetic analysis.

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.

Retinitis Punctata Albescens and RLBP1-Allied Phenotypes: Phenotype-Genotype Correlation and Natural History in the Aim of Gene Therapy.

Purpose: To identify relevant criteria for gene therapy based on clinical and genetic characteristics of rod-cone dystrophy associated with RLBP1 pathogenic variants in a large cohort comprising children and adults. Design: Retrospective cohort study. Participants: Patients with pathogenic variants in RLBP1 registered in a single French reference center specialized in inherited retinal dystrophies. Methods: Clinical, multimodal imaging, and genetic findings were reviewed. Main Outcome Measures: Age of onset; visual acuity; ellipsoid line length; nasal, temporal, and foveal retinal thickness; and pathogenic variants and related phenotypes, including Newfoundland rod-cone and Bothnia dystrophies (NFRCDs), were reappraised. Results: Twenty-one patients (15 families) were included. The most frequent form was NFRCD with 12 patients (8 families) homozygous for the recurrent deletion of exons 7 through 9 in RLBP1 and 5 patients (4 families) with biallelic protein-truncating variants (2 novel: p.Gln16∗ and p.Tyr251∗). A novel combination of the p.Arg234Trp Bothnia variant with a nonsense variant in trans led to Bothnia dystrophy in 2 sisters. One proband carrying the p.Met266Lys Bothnia variant and in trans p.Arg121Trp and a second, with the p.Arg9Cys and p.Tyr111∗ combination, both demonstrated mild retinitis punctata albescens. Independently of genotype, all patients showed a visual acuity of worse than 20/200, an ellipsoid line width of less than 1000 µm, and a mean foveal thickness of less than 130 to 150 µm, with loss of both the interdigitation and ellipsoid lines. Conclusions: The eligibility for RLBP1 gene therapy first should be determined according to the biallelic variant combination using a robust classification as proposed herein. An ellipsoid line width of more than 1200 µm and a central thickness of more than 130 to 150 µm with detectable ellipsoid and interdigitation lines should be 2 prerequisite imaging indicators for gene therapy.

Belatacept associated - cytomegalovirus retinitis in a kidney transplant recipient: a case report and review of the literature.

BACKGROUND: To report the first case of belatacept-associated multidrug-resistant Cytomegalovirus retinitis in a kidney transplant recipient. CASE PRESENTATION: A 76-year-old African male renal allograft recipient was admitted for acute visual loss of the right eye. Ophthalmological examination of the right eye showed anterior uveitis and vitritis associated with large paravascular haemorrhages and yellow necrotic borders, involving the posterior pole but not the fovea. Both Cytomegalovirus DNA in plasma and aqueous humor were positive. The patient had had several episodes of Cytomegalovirus reactivation subsequent to the introduction of belatacept. His cytomegalovirus was multi-drug resistant, and was treated with maribarir, intravitreal and systemic injections of foscarnet, and anti-Cytomegalovirus human immunoglobulin. In parallel, belatacept was stopped and switched to tacrolimus. Cytomegalovirus DNA became undetectable and there was partial improvement of visual acuity at the last ophthalmologic examination, 18 months after the initial diagnosis of Cytomegalovirus retinitis. CONCLUSION: Cytomegalovirus retinitis is an uncommon opportunistic infection in kidney transplant recipients. Cytomegalovirus retinitis is a serious infection because of the risk of blindness and the occurrence of associated life-threatening opportunistic infections. In view of the recent literature, kidney transplant recipients treated by belatacept immunosuppression may be at increased risk for Cytomegalovirus disease, notably Cytomegalovirus retinitis. The occurrence of Cytomegalovirus retinitis may help improve the selection of patients converted to belatacept.