The Role of Subretinal Injection in Ophthalmic Surgery: Therapeutic Agent Delivery and Other Indications.

Subretinal injection is performed in vitreoretinal surgery with two main aims, namely, the subretinal delivery of therapeutic agents and subretinal injection of fluid to induce a controlled and localized macular detachment. The growing interest in this technique is mainly related to its suitability to deliver gene therapy in direct contact with target tissues. However, subretinal injection has been also used for the surgical management of submacular hemorrhage through the subretinal delivery of tissue plasminogen activator, and for the repair of full-thickness macular holes, in particular refractory ones. In the light of the increasing importance of this maneuver in vitreoretinal surgery as well as of the lack of a standardized surgical approach, we conducted a comprehensive overview on the current indications for subretinal injection, surgical technique with the available variations, and the potential complications.

Choroidal and peripapillary changes in high myopic eyes with Stickler syndrome.

BACKGROUND: To compare different clinical and Spectral-Domain Optical Coherence Tomography (SD-OCT) features of high myopic eyes with Stickler syndrome (STL) with matched controls. METHODS: Patients with genetically confirmed STL with axial length ≥ 26 mm and controls matched for axial length were included. The following data were obtained from SD-OCT scans and fundus photography: choroidal and retinal thickness (respectively, CT and RT), peripapillary atrophy area (PAA), presence of posterior staphyloma (PS). RESULTS: Twenty-six eyes of 17 patients with STL and 25 eyes of 19 controls were evaluated. Compared with controls, patients with STL showed a greater CT subfoveally, at 1000 µm from the fovea at both nasal and temporal location, and at 2000 and 3000 µm from the fovea in nasal location (respectively, 188.7±72.8 vs 126.0±88.7 µm, 172.5±77.7 vs 119.3±80.6 µm, 190.1±71.9 vs 134.9±79.7 µm, 141.3±56.0 vs 98.1±68.5 µm, and 110.9±51.0 vs 67.6±50.7 µm, always P< 0.05). Furthermore, patients with STL showed a lower prevalence of PS (11.5% vs 68%, P< 0.001) and a lower PAA (2.2±2.1 vs 5.4±5.8 mm2, P=0.03), compared with controls. CONCLUSIONS: This study shows that high myopic patients with STL show a greater CT, a lower PAA and a lower prevalence of PS, compared with controls matched for axial length. These findings could be relevant for the development and progression of myopic maculopathy in patients with STL.

Preoperative Optical Coherence Tomography Findings of Foveal-Splitting Rhegmatogenous Retinal Detachment.

PURPOSE: To assess preoperative optical coherence tomography (OCT) findings of foveal-splitting retinal detachment (RD) and determine postoperative outcomes. METHODS: Consecutive patients who underwent RD surgery over a 1-year period were included. Patients diagnosed with a detachment extending to the edge of the fovea on fundus examination (i.e., macula-On/Off) underwent macular OCT scanning. Visual acuity (VA) after 1 year of macula-On/Off, macula-On, and macula-Off eyes was compared. RESULTS: A total of 85 eyes were included, 8 of which had a macula-On/Off RD. On preoperative OCT, all macula-On/Off RD eyes had foveal detachment extending beyond the foveal center over a median distance of 632 µm. Mean VA of the macula-On/Off eyes had improved from 20/160 to 20/40 at 1 year postoperatively (p = 0.035). The preoperative VA of macula-On/Off eyes was significantly better than macula-Off eyes (p = 0.032) and lower than macula-On eyes (p = 0.004). At 1 year, the VA of macula-On/Off eyes was no different from that of the macula-On eyes (p = 0.320), and tended to be better than that of the macula-Off eyes (p = 0.062). CONCLUSION: Preoperative OCT revealed a shallow RD extending beyond the foveal center in eyes with clinical foveal-splitting RD. These eyes, termed macula-On/Off RD eyes, had a preoperative VA between macula-On and macula-Off eyes, while their final VA was close to those with macula-On RD.

New clinical forms of hereditary apoA-I amyloidosis entail both glomerular and retinal amyloidosis.

Apolipoprotein A1 amyloidosis (ApoAI) results from specific mutations in the APOA1 gene causing abnormal accumulation of amyloid fibrils in diverse tissues. The kidney is a prominent target tissue in ApoAI amyloidosis with a remarkable selectivity for the renal medulla. Here, we investigated six French families with ApoAI Glu34Lys, p.His179Profs∗47, and a novel p.Thr185Alafs∗41 variant revealing unprecedented clinical association of a glomerular with a retinal disease. Comprehensive clinicopathological, molecular and proteomics studies of numerous affected tissues ensured the correlation between clinical manifestations, including novel unrecognized phenotypes, and apoA-I amyloid deposition. These ophthalmic manifestations stemmed from apoA-I amyloid deposition, highlighting that the retina is a previously unrecognized tissue affected by ApoAI amyloidosis. Our study provides the first molecular evidence that a significant fraction of ApoAI amyloidosis cases with no family history result from spontaneous neomutations rather than variable disease penetrance. Finally, successful hepatorenal transplantation resulted in a life- and vision-saving measure for a 32-year-old man with a hitherto unreported severe ApoAI amyloidosis caused by the very rare Glu34Lys variant. Our findings reveal new modes of occurrence and expand the clinical spectrum of ApoAI amyloidosis. The awareness of glomerular and ocular manifestations in ApoAI amyloidosis should enable earlier diagnosis and avoid misdiagnosis with other forms of renal amyloidosis. Thus, documented apoA-I amyloid deposition in the retina offers new biological information about this disease and may change organ transplantation practice to reduce retinal damage in patients with ApoAI amyloidosis.

PREOPERATIVE FACTORS INFLUENCING VISUAL RECOVERY AFTER VITRECTOMY FOR MYOPIC FOVEOSCHISIS.

PURPOSE: To determine the preoperative factors influencing visual recovery after vitrectomy for myopic foveoschisis. METHODS: Sixty-six eyes of 65 consecutive patients operated on for myopic foveoschisis were retrospectively included. All eyes underwent a preoperative ocular examination including best-corrected visual acuity (BCVA) and spectral domain optical coherence tomography with central foveal thickness measurement and foveal status classification: simple foveoschisis, foveal detachment, or macular hole. To study the impact of preoperative visual acuity, 4 visual acuity groups separated by quartile ranges were defined. Postoperative visits at 1, 3, or 12 months including BCVA measurement and optical coherence tomography were recorded. RESULTS: Mean refraction was -15.90 diopters, mean axial length was 30.30 mm, mean central foveal thickness was 590 µm, and mean baseline logarithm of the maximum angle of resolution visual acuity was 0.68 (Snellen equivalent of 20/96). The final BCVA improved significantly from 3 months after surgery until the last follow-up visit; the mean logarithm of the maximum angle of resolution visual acuity at last follow-up was 0.43 (Snellen equivalent of 20/54). Mean central foveal thickness decreased significantly as soon as the first postoperative month (P < 0.0001). The preoperative BCVA was the only independent factor significantly correlated with the final BCVA as opposed to the foveal status (P < 0.0001). The mean BCVA and mean visual gain at the last follow-up visit were significantly different between the four visual acuity groups (P < 0.0001 and P = 0.017, respectively). CONCLUSION: The main factor influencing the postoperative visual acuity is the preoperative visual acuity. Although the preoperative anatomical status seemed important in surgeon decision making, once normalized on visual acuity, it no longer influenced the postoperative visual acuity.

Deletions Overlapping VCAN Exon 8 Are New Molecular Defects for Wagner Disease.

Wagner disease is a rare nonsyndromic autosomal-dominant vitreoretinopathy, associated with splice mutations specifically targeting VCAN exon 8. We report the extensive genetic analysis of two Wagner probands, previously found negative for disease-associated splice mutations. Next-generation sequencing (NGS), quantitative real-time PCR, and long-range PCR identified two deletions (3.4 and 10.5 kb) removing at least one exon-intron boundary of exon 8, and both correlating with an imbalance of VCAN mRNA isoforms. We showed that the 10.5-kb deletion occurred de novo, causing somatic mosaicism in the proband's mother who had an unusually mild asymmetrical phenotype. Therefore, exon 8 deletions are novel VCAN genetic defects responsible for Wagner disease, and VCAN mosaic mutations may be involved in the pathogenesis of Wagner disease with attenuated phenotype. NGS is then an effective screening tool for genetic diagnosis of Wagner disease, improving the chance of identifying all disease-causative variants as well as mosaic mutations in VCAN.

Evolution of Subfoveal Detachments Secondary to Idiopathic Epiretinal Membranes after Surgery.

PURPOSE: To study the characteristics of subfoveal abnormalities secondary to idiopathic epiretinal membranes (ERM) using improved-resolution spectral-domain optical coherence tomography (SD OCT) and their evolution after surgery. DESIGN: Retrospective, observational cohort study. PARTICIPANTS: The files of 344 patients operated on consecutively for ERM over a 2-year period in a single tertiary ophthalmologic center were reviewed. Patients with vitreomacular traction syndrome, secondary ERM, or both were excluded. METHODS: In all, 293 eyes with idiopathic ERM were included in the final analysis. Fundus photographs were reviewed to assess the presence of a yellow foveal spot, and SD OCT analysis was performed. MAIN OUTCOME MEASURES: Presence or absence of a subfoveal abnormality and its SD OCT characteristics before and after surgery at 1 month, 3 months, and at final visit; best-corrected visual acuity (BCVA) and central macular thickness at baseline, 1 month, 3 months, and at the final visit. RESULTS: Before surgery, a subfoveal detachment (SD) corresponding to the yellow deposit was present in 59 of 293 eyes (20%). No difference was found for the postoperative BCVA between the 59 eyes with SD before surgery and the 234 eyes without SD (0.253 ± 0.14 logarithm of the minimum angle of resolution [logMAR] vs. 0.262 ± 0.24 logMAR, respectively; P = 0.6). Sixty-eight percent (n = 40/59) of SD disappeared after surgery during a mean follow-up of 4.8 ± 3.2 months, most of them (62%) before month 3. Among eyes with preoperative SD, no difference was found for the postoperative BCVA between eyes with disappeared SD and those with persistent SD. CONCLUSIONS: Subfoveal detachments secondary to idiopathic ERM were observed in 20% of these eyes. They disappeared after surgery in more than two thirds of cases, usually early during postoperative course. Subfoveal detachments do not affect visual outcome and should not interfere with surgical decision making.

SPIRONOLACTONE FOR NONRESOLVING CENTRAL SEROUS CHORIORETINOPATHY: A RANDOMIZED CONTROLLED CROSSOVER STUDY.

PURPOSE: To evaluate the effect of spironolactone, a mineralocorticoid receptor antagonist, for nonresolving central serous chorioretinopathy. METHODS: This is a prospective, randomized, double-blinded, placebo-controlled crossover study. Sixteen eyes of 16 patients with central serous chorioretinopathy and persistent subretinal fluid (SRF) for at least 3 months were enrolled. Patients were randomized to receive either spironolactone 50 mg or placebo once a day for 30 days, followed by a washout period of 1 week and then crossed over to either placebo or spironolactone for another 30 days. The primary outcome measure was the changes from baseline in SRF thickness at the apex of the serous retinal detachment. Secondary outcomes included subfoveal choroidal thickness and the ETDRS best-corrected visual acuity. RESULTS: The mean duration of central serous chorioretinopathy before enrollment in study eyes was 10 ± 16.9 months. Crossover data analysis showed a statistically significant reduction in SRF in spironolactone treated eyes as compared with the same eyes under placebo (P = 0.04). Secondary analysis on the first period (Day 0-Day 30) showed a significant reduction in subfoveal choroidal thickness in treated eyes as compared with placebo (P = 0.02). No significant changes were observed in the best-corrected visual acuity. There were no complications related to treatment observed. CONCLUSION: In eyes with persistent SRF due to central serous chorioretinopathy, spironolactone significantly reduced both the SRF and the subfoveal choroidal thickness as compared with placebo.

Is it safe to use telephone for anaesthesia consultation in high-risk patients before non-invasive surgery? A pilot study in ophthalmology.

BACKGROUND: Although telemedicine with video support for preoperative evaluation has been found effective, there is limited research on anaesthesia consultation by phone without video support, particularly among high-risk patients. To evaluate the effectiveness, safety and potential benefits of performing pre-anaesthesia evaluation by phone before eye surgery in patients having non-invasive surgery, we performed an observational study in a French teaching hospital. METHOD: All elective patients having elective ophthalmic surgery were included to have a consultation by phone instead of an in-person consultation, regardless of the type of anaesthesia or ASA score. The incidence of day-of-surgery cancellations, patient satisfaction and time/distance saved through phone consultations were assessed. RESULTS: From February to October 2022, data of 3480 patients were analyzed, including 370 (11%) high-risk patients (ASA 3-4). Anaesthesia-related day-of-surgery cancellation rate was 0.5% (n = 20) due to non-compliance with pre-operative instructions. No cancellation was due to inadequate pre-operative evaluation. No difference in cancellation rate was observed between low-risk patients and high-risk patients. Telephone consultations saved patients a mean of 126 min and 86 km. A younger age, an active status and living far from the hospital were associated with phone consultation preference. CONCLUSION: Phone anaesthesia consultation seems to be effective and safe before ophthalmic surgery, regardless of patient's perioperative risk. In addition, phone consultation provides significant time and distance savings. Our results must be confirmed through a multicentric randomised study comparing phone and traditional consultation in ophthalmology as well as in other non-invasive surgical procedures in a high-risk patients population.

MACULAR ATROPHY AFTER MACULAR HOLE SURGERY ASSISTED BY MEMBRANE BLUE DUAL: A CASE SERIES.

PURPOSE: The aim of this study is to describe the clinical and multimodal imaging findings in patients with macular atrophy after macular hole surgery assisted by Membrane Blue Dual. METHOD: This study is a monocenter, retrospective, observational case series that included patients who presented with macular atrophy following macular hole surgery. RESULTS: Among the patients included in this study, four were operated for idiopathic macular hole and one for total retinal detachment associated with macular hole. In all patients, the internal limiting membrane was brittle and adherent, and multiple stains were required. One month postoperatively, all patients showed a reduced visual acuity except the patient with total retinal detachment. At fundus examination all patients showed patchy atrophy with a mottled hypopigmented and hyperpigmented appearance in the macular region. Optical coherence tomography scans demonstrated a closed macular hole with retinal thinning, disruption of the external retinal layers, and irregular retinal pigment epithelium thickening. Fundus autofluorescence showed a well-defined area of both hypoautofluorescence and hyperautofluorescence involving the macular area. CONCLUSION: Macular atrophy after Membrane Blue Dual-assisted internal limiting membrane peeling represents a severe complication that vitreoretinal surgeons should be aware of and that should be taken into account in preoperative evaluation and surgical procedure planning. To reduce the risk of this complication, we recommend to ensure the best conditions of visibility, to reduce as much as possible the intensity and the distance of the endoillumination from the retina, and to use as little dye as possible.

Multimodal imaging in early onset non-neovascular pigment epithelial detachments.

PURPOSE: To describe multimodal imaging of two cases of bilateral non-vascularized pigment epithelial detachments (PED) in young patients with a long-term follow-up. METHODS: A complete ophthalmological examination was performed at each follow-up visit including best corrected visual acuity (BCVA), intraocular pressure, slit lamp examination, spectral domain optical coherence tomography (SD-OCT), fluorescein and indocyanine green angiography, OCT angiography. RESULTS: Multimodal imaging of two women presenting avascular PED, aged 43 and 57, respectively, was described. In both patients, SD-OCT revealed a high central macular hyporeflective elevation corresponding with PED. Both patients showed a choroidal layer thicker than 420 µm. Fluorescein and indocyanine green angiography didn't show any choroidal neovascularization either at early or late frames. Cross-sectional and en face optical coherence tomography angiography (OCTA) didn't show any flow beneath the PED. During the follow up period one eye showed a retinal pigment epithelium tear and all eyes showed the presence of apical sub-retinal fluid and hyperreflective material on the top of the PED. None of the two patients showed any sign of atrophy during the follow-up period. CONCLUSION: The peculiar characteristics of the presented cases suggest that specific pathogenetic mechanisms, not necessarily related to age related macular degeneration, may play a key role in the development of these lesions. Whether early onset of such drusenoid PED is a specific entity resulting from a genetic deficit of lipid transporters in the RPE is unknown. Further genetic and metabolic studies should be conducted.

A family with Wagner syndrome with uveitis and a new versican mutation.

PURPOSE: To report the clinical and molecular findings of a kindred with Wagner syndrome (WS) revealed by intraocular inflammatory features. METHODS: Eight available family members underwent complete ophthalmologic examination, including laser flare cell meter measurements. Collagen, type II, alpha 1, versican (VCAN), frizzled family receptor 4, low density lipoprotein receptor-related protein 5, tetraspanin 12, and Norrie disease (pseudoglioma) genes were screened with direct sequencing. RESULTS: The index case was initially referred for unexplained severe and chronic postoperative bilateral uveitis following a standard cataract surgery procedure. Clinical examination of the proband revealed an optically empty vitreous with avascular vitreous strands and veils, features highly suggestive of WS. The systematic familial ophthalmologic examination identified three additional unsuspected affected family members who also presented with the WS phenotype, including uveitis for one of them. We identified a novel c.4004-6T>A nucleotide substitution at the acceptor splice site of intron 7 of the VCAN gene that segregated with the disease phenotype. CONCLUSIONS: We present a family with WS with typical WS features and intraocular inflammatory manifestations associated with a novel splice site VCAN mutation. Beyond the structural role in the retinal-vitreous architecture, versican is also emerging as a pivotal mediator of the inflammatory response, supporting uveitis predisposition as a clinical manifestation of WS.

Ranibizumab for choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy: one-year results.

PURPOSE: To evaluate the efficacy of intravitreal injections of ranibizumab for choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy. METHODS: Retrospective case series of 24 eyes affected with choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy treated by intravitreal injections of ranibizumab (0.5 mg/0.05 mL). Best-corrected visual acuity, fundus examination, spectral domain optical coherence tomography, fundus autofluorescence, and fluorescein and indocyanine green angiography were performed for the diagnosis of adult-onset foveomacular vitelliform dystrophy and choroidal neovascularization. After initial 3 monthly injections of ranibizumab, patients were followed up monthly and retreated if neovascular activity persisted. Outcome measure was the proportion of patients losing fewer than 3 lines of visual acuity from baseline to 12 months (final visit). RESULTS: At final visit, the mean number of ranibizumab injections was 4.5 ± 1.29. From baseline to final visit, 21 of 24 eyes (87.5%) lost fewer than 3 lines of visual acuity. Mean best-corrected visual acuity did not change significantly from baseline to final visit (0.37 ± 0.2 logarithm of the minimum angle of resolution vs. 0.30 ± 0.25 logarithm of the minimum angle of resolution, respectively; P = 0.115). Mean central macular thickness significantly decreased from baseline to final visit (327 ± 83 µm vs. 260 ± 57 µm, respectively; P = 0.001). CONCLUSION: In this series, ranibizumab succeeded in stabilizing best-corrected visual acuity in patients with choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy. Ranibizumab seems to be a reasonable therapeutic option in this condition.

Investigating pupillometry to detect preoperative anxiety: a pilot study.

Guidelines from the European Society of Anesthesia (ESA) insist on the importance of preoperative anxiety management. However, its assessment currently relies on questionnaires that are long to submit and sometimes difficult to interpret. Exploring the balance between sympathetic and parasympathetic neural systems through the use of pupillometry is a promising path to identify anxiety and thus provides an objective and reproducible assessment tool. A single-center prospective observational study was conducted in a population of ambulatory ophthalmological surgery patients. Preoperative anxiety was assessed using the Surgical Fear Questionnaire (SFQ). Measurements were taken using an Algiscan® (IDMed) type pupillometer before, during, and after insertion of the peripheral IV catheter. A statistical correlation test was carried out between the different evaluations of anxiety and the coefficient of variation of the pupillary diameter (VCPD). A total of 71 patients were included in the study between July 2020 and February 2021, with a median SFQ score of 23 [IQR 11-34]. No significant statistical correlation was found between the baseline pupillary diameter, or VCPD, and preoperative anxiety levels. Similarly, the pupillometric variables did not differ significantly when adjusting for the level of anxiety during and after painful stimulation due to canulation. More studies are necessary to explore the potential correlation between preoperative anxiety and pupillometry.

Risk Factors of Cystoid Macular Edema After Pars Plana Vitrectomy for Pseudophakic Retinal Detachment.

INTRODUCTION: This study aimed to investigate the prevalence of cystoid macular edema after pars plana vitrectomy for the treatment of pseudophakic rhegmatogenous retinal detachment and identify possible related risk factors. METHODS: A retrospective monocentric study was conducted within a cohort of pseudophakic patients undergoing vitrectomy for rhegmatogenous retinal detachment between January 2019 and December 2022. Demographic data, initial and intraoperative characteristics of rhegmatogenous retinal detachment, and postoperative data were analyzed. Cystoid macular edema was defined on optical coherence tomography exclusively. RESULTS: A total of 164 eyes of 164 patients were included for analysis. The mean age of the patients at surgery was 65.7 ± 12.0 years. The mean best-corrected visual acuity was 2.1 ± 1.0 logMAR preoperatively and 1.0 ± 0.7 logMAR postoperatively. The mean follow-up was 13.4 ± 7.7 months. The prevalence of cystoid macular edema was 17.1% [9.8-26.4]. In multivariate analysis, severe proliferative vitreoretinopathy (relative risk 3.6 [1.3-9.7]) and laser retinopexy (relative risk 8.4 [1.1-64.7]) were independently and significantly associated with cystoid macular edema. CONCLUSION: The prevalence of cystoid macular edema in pseudophakic rhegmatogenous retinal detachment after pars plana vitrectomy was 17.1%. Severe proliferative vitreoretinopathy stage and the use of endolaser retinopexy were independent risk factors for development of cystoid macular edema.

The StarvAnx Study-Comparison Between the Effects of Non-fasting Vs. Fasting Strategy on Surgical Outcomes, Anxiety and Pain in Patients Undergoing Cataract Surgery Under Topical Anesthesia: A Randomized, Crossover, Controlled Trial.

Background: Fasting is usually recommended in patients undergoing cataract surgery under topical anesthesia. However, starving before surgery may increase preoperative anxiety and affect surgical outcomes. It is not known which fasting or non-fasting strategy is best for cataract surgery. The aim of this study was to compare non-fasting and fasting strategy in patients undergoing cataract surgery under topical anesthesia with regard to surgical outcomes, anxiety and pain. Methods: This randomized, crossover, controlled trial enrolled patients undergoing surgery for bilateral cataract under topical anesthesia at Cochin Hospital (Paris, France), from February to May 2021. Patients were randomly assigned to the non-fasting or fasting group for the first eye surgery and were switched to the other group for the second eye surgery. The primary endpoint was to compare the rate of anesthetist's interventions during surgery. The secondary endpoints included intra-operative complications, duration of surgery, surgeon perception of surgical difficulty, anesthesia-related complications and anxiety and pain level. Results: one hundred and nine consecutive patients were included, with 60 of them being fasted first and non-fasted for the second eye surgery, while the other 59 were non-fasted first and fasted for the next surgery. The number of patients requiring sedation was significantly lower in the non-fasting group compared with the fasting group [1%; 95%IC (0-3.2) vs. 6%; 95%IC (2.9-8.9), P = 0.04]. No anesthesia-related complications were observed. There was no difference in the number of intra-operative complications between the non-fasting and the fasting groups (,respectively, 0 and 1; P = 1). Anxiety level and surgical pain were significantly lower in the non-fasting group compared to the fasting group (,respectively, 2.3 ± 2.0 vs. 4.1 ± 2.4, P = 0.01 and 0.6 ± 0.6 vs. 2.6 ± 3.4, P = 0.003). The mean duration of surgery was significantly shorter in the non-fasting group compared with the fasting group (,respectively, 16.0 ± 5.9 vs. 22.3 ± 6.1 min; P = 0.03). Conclusion: In conclusion pre-operatory non-fasting strategy provides a better patient experience with regards to preoperative anxiety and surgical pain. It allows to reduce operating times and is safe and well-tolerated as regards the anesthetic intervention.