Could internal limiting membrane peeling before Voretigen neparvovec-ryzl subretinal injection prevent focal chorioretinal atrophy?

Purpose: To report the effect of internal limiting membrane (ILM) peeling prior to Voretigen Neparvovec-ryzl (VN) subretinal injection on focal chorioretinal atrophy development in patients presenting with RPE65-mediated Leber congenital amaurosis (LCA). Design: Retrospective case series. Methods: Three patients who underwent bilateral subretinal VN injection for RPE65-mediated LCA were followed up for 18-24 months. ILM peeling was performed unilaterally in patients 1 and 2 and bilaterally in patient 3. Chorioretinal atrophy was identified on fundus biomicroscopy, non-mydriatic retinography and/or ultrawide field fundus imaging. Best corrected visual acuity (BCVA), spectral-domain optical coherence tomography (SD-OCT), visual fields, full-field stimulus threshold (FST) and visual functioning questionnaire score (NEI-VFQ-25) were reported. Outcome measures were changes in BCVA, visual fields, FST, NEI-VFQ-25, and chorioretinal atrophy location. Results: Chorioretinal atrophy at the injection site exclusively developed in eyes which did not undergo prior ILM peeling. In patient 3, bilateral pre-operative nummular chorioretinal alterations progressed toward epithelial atrophic patches in the mid and extreme retinal periphery 18 months after VN injection. BCVA and visual fields improved bilaterally. NEI_VFQ 25 remained stable in patient 1 and improved in patient 2 and 3. FST test improved bilaterally in patient 3. Conclusions: ILM peeling prior to VN injection seems to be a smoother and safer technique to administer VN treatment and may prevent secondary focal atrophy development at the injection site. However, another type of more extended chorioretinal atrophy might exist and could be related to LCA evolution or to incompletely understood adverse effect of VN product.

Telangiectatic capillaries causing persistent diabetic macular edema successfully treated by photodynamic therapy.

PURPOSE: To report two cases of persistent macular edema caused by the exudation of diabetic telangiectatic capillaries (TelCaps) which have been successfully treated with photodynamic therapy (PDT). METHODS: review of data from two patients suffering from persistent macular edema caused by parafoveolar TelCaps. In both cases, conventional laser was impossible, because TelCaps were to close from foveal center. RESULTS: The use of focal PDT on perifoveolar TelCaps permitted to reduce persistent macular edema and to avoid inefficient intra-vitreal anti-vascular epithelial growth factor (anti-VEGF) or steroid injections. In both cases, visual acuity was fully restored four to six months after PDT. Central Macular Thickness was also normalized in the first case and significantly reduced in the second case. In both cases, visual gain was sustained throughout the whole follow-up period (2 and 1 year respectively). CONCLUSION: PDT can be helpful to treat diabetic macular edema caused by TelCaps non-responding to approved intravitreal therapy or for which conventional laser is contraindicated.

Extraocular muscle ductions following nasal transposition of the split lateral rectus muscle.

OBJECTIVE: To quantify changes in ductions following nasal transposition of the split lateral rectus muscle (NTSLR) for treating third nerve palsy. DESIGN: Retrospective cohort study. PARTICIPANTS: A single eye from each patient with third nerve palsy treated with NTSLR with ocular motility measurements. METHODS: Observation of changes in pre- and postoperative ductions. Outcome measures including patient demographic and surgical factors associated with the ability to adduct beyond the midline after NTSLR were evaluated using multivariable logistic regression. RESULTS: A total of 116 patients met the inclusion criteria for this study. The NTSLR significantly decreased abduction (median of 0 limitation [interquartile range (IQR), 0-0] prior to surgery to -4 [IQR, -4 to -3] after NTSLR; p < 0.001), with a corresponding improvement in adduction (median, -5 [IQR, -5 to -4] prior to surgery to -4 [IQR, -4 to -3] after NTSLR; p < 0.001). There was no change in median supraduction or infraduction after NTSLR (p > 0.05). The ability to adduct beyond the midline after NTSLR was demonstrated in 42% of patients. Although not statistically significant, a trend toward a postoperative ability to adduct beyond the midline was seen in patients who had concurrent superior oblique muscle tenotomy (odds ratio [OR] = 5.08; 95% CI, 0.91-40.9) or who were designated with partial rather than complete third nerve palsy (OR = 2.29; 95% CI, 0.82-6.70). CONCLUSIONS: NTSLR improves the horizontal midline positioning of eyes with third nerve palsy. Most eyes lose the ability to abduct, but some regain a modest ability to adduct while vertical ductions remain unchanged.

LONG-TERM MICROVASCULAR REMODELING AND CYSTIC CHANGES AFTER RETINAL DETACHMENT TREATED WITH SILICON OIL TAMPONADE.

PURPOSE: To determine the long-term microvascular alterations associated with macular cystic changes after retinal detachment surgery with silicone oil tamponade. METHODS: The results of two optical coherence tomography angiographies performed at 11 months and 38 months after silicone removal were retrospectively analyzed for 30 eyes. The data were compared between both measurements and between eyes with macular cysts (MC+) and without macular cysts (MC-). Two patterns of cysts were identified and compared: cysts exclusively involving the inner nuclear layer (INLc) and cysts present in all retinal layers. RESULTS: At both end points, 20 eyes (67%) presented with macular cysts, 12 of them (40%) had INLc. At the first end point, vascular density of superficial capillary plexus was higher and superficial foveal avascular zone was smaller in MC+ eyes than in MC- eyes (P = 0.04 and P = 0.017, respectively). At the second end point, vascular density of superficial capillary plexus significantly decreased in MC+ eyes as compared with the first end point (P < 0.001) and superficial foveal avascular zone enlarged (P < 0.001). Macular central thickness decreased between follow-ups only in eyes with INLc (P < 0.01). The final best-corrected visual acuity was better in eyes with INLc than in eyes with cysts present in all retinal layers (P < 0.01). There was no difference between the final best-corrected visual acuity in eyes with INLc and MC- eyes. CONCLUSION: Macular cysts are a common finding long after silicon removal. Vascular remodeling seems characterized by an initial increase of the vascular density of superficial capillary plexus in eyes with cysts, which is followed by its progressive decrease. The INLc is the most common pattern of cysts. They are associated with a progressive decrease of the central macular thickness without visual impairment.

Development and validation of a new method for visual acuity assesment on tablet in pediatric population: eMOVA test.

BACKGROUND: Amblyopia is a major public health concern. Its screening and management require reliable methods of visual acuity assessment. New technologies offer nowadays many tests available on different app stores for smartphone or tablet but most of them often lack of scientific validation for a medical use. The aim of our study was to attempt validating a tablet-based near visual acuity test adapted to the pediatric population: the eMOVA test (electronic Measurement Of Visual Acuity) by comparing visual acuity measured with more conventional test. METHODS: A cohort of 100 children aged 3 to 8 attending the ophthalmic-pediatric for eye examination between September 2016 and June 2017 were included in the study. Near visual acuity was assessed on participants using both the eMOVA test and a Standard test (Rossano-Weiss test). Duration of each test, its comprehension, its acceptability and the attention of the child during the test was also investigated. RESULTS: The eMOVA test overestimated near visual acuity by 0.06 logMAR. This difference, statistically significant, was not clinically relevant. The duration of the eMOVA test was longer than the reference test, but less discomfort and preferred by children and their parents compared to standard tests. CONCLUSION: The eMOVA test appears as a reliable test to assess near visual acuity in children. By its portability and efficiency, this application proved to be a relevant tool to be used for children eye examination in daily routine at the hospital.

OCT-Angiography for Detection of Choroidal Neovascularization: A Retrospective Real-Life Study.

PURPOSE: The purpose of the study was to assess OCT-angiography (OCT-A) contribution for choroidal neovascularization (CNV) detection, with respect to multimodal imaging (MMI) modality (including OCT, fluorescein angiography (FFA), and indocyanine green angiography [ICG]), in a real-life consultation practice. METHODS: Data of all consecutive patients undergoing OCT-A examination for CNV suspicion were collected between September 2017 and September 2019 at Strasbourg University Hospital, France. Only eyes which had anti-VEGF injection in the last 3 months were excluded. All types of neovascularization were included. For all patients, data from OCT, OCT-A, FFA, and ICG were interpreted by residents and retinal specialists, independently. Final diagnosis of CNV was based on decision to treat. Sensibility, specificity, and predictive values were computed for OCT-A alone and for MMI (OCT combined to angiography). They were computed for each group. OCT-A was also assessed as "contributory" (i.e., assessing without doubt the presence or absence of CNV) or not, with respect to MMI. RESULTS: In total, 161 eyes of 145 patients were included. MMI sensibility was better than OCT-A sensibility (93.8 vs. 65.6%). OCT-A specificity was better than MMI specificity (96.9 vs. 89.5%). OCT-A was essential for diagnosis in 16.9% of cases. Sensibility and specificity values for all exams were better when interpreted by retinal specialists than residents. OCT-A was judged "contributory" in 57.4% of eyes. OCT-A was significantly less contributory when artefacts were present (32.9% of eyes with artefacts vs. 63.5% without, p < 0.001). CONCLUSION: OCT-A showed to be essential in diagnosing CNV in >16% of cases. However, it often failed to conclude for the absence of CNV, which obliged to perform more exams such as angiography. OCT-A must be part of diagnostic procedure for CNV detection but does not discard angiography in everyday life practice.

[Screening for visual disturbances in children]. / Dépistage des troubles visuels chez l'enfant.

"Screening for visual disturbances in children.Vision screening in children is a public health concern, as untreated visual disorders may have irreversible consequences, as well as an important social, scholar, and financial impact. Moreover, most of these disturbances such as refractive errors or strabismus can easily be corrected. Guidelines to improve the screening were recently issued by a French expert group (AFSOP). They emphasize the importance of an ophthalmological examination for children at risk of organic and functional amblyopia, respectively during the first week or first year of life. They also recommend a systematic screening for amblyopia, refractive errors or strabismus in general population at age 3, using three different tests. In addition, warning signs such as a leukocoria or a buphthalmia should be recognized by every physician and addressed immediately for an extensive ophthalmo- logical examination."

"Dépistage des troubles visuels chez l'enfant. Le dépistage visuel chez l'enfant représente un objectif de santé publique en raison de l'impact social, scolaire et financier d'une anomalie de la vision, potentiellement irréversible en l'absence de prise en charge précoce. De plus, la plupart de ces troubles sont corrigibles, c'est le cas notamment des anomalies de la réfraction et du strabisme. Un groupe d'experts de l'Association francophone de strabologie et d'ophtalmologie pédiatrique (AFSOP) a récemment mis à jour des recommandations consensuelles pour l'optimisation de ce dépistage. Ce travail souligne l'importance d'un examen ophtalmologique rapide dans la première semaine ou première année de vie respectivement pour les enfants à risque d'amblyopie organique et fonctionnelle, ainsi que d'un dépistage systématique de tous les enfants à l'âge de 3 ans à l'aide de trois examens visant à détecter respectivement un trouble de la réfraction, un strabisme ou une amblyopie. Par ailleurs, certains signes d'appel, comme la présence d'une leucocorie ou d'une buphtalmie, conduisant à un examen ophtalmologique sans délai, doivent être reconnus par tout professionnel en charge de l'examen global de l'enfant."

VISUAL IMPAIRMENT AND MACULAR VASCULAR REMODELING SECONDARY TO RETROGRADE MACULOPATHY IN RETINAL DETACHMENT TREATED WITH SILICON OIL TAMPONADE.

PURPOSE: To assess the frequency of macular cysts (MCs) in retinal detachment treated with silicone oil and evaluate their impact on visual acuity and macular vascularization using optical coherence tomography-angiography. METHODS: Forty-three eyes of 41 patients treated with silicone oil for retinal detachment were retrospectively studied. Best-corrected visual acuity and 6- × 6-mm optical coherence tomography-angiography examination at least 3 months after silicone oil removal were reviewed. In eyes with MCs, cyst area was measured on the en face optical coherence tomography-angiography image using ImageJ. Density of superficial capillary plexus and area of superficial foveal avascular zone were generated by the optical coherence tomography-angiography. Density of deep capillary plexus and deep foveal avascular zone area were measured using ImageJ. RESULTS: Twenty-five eyes (58%) presented with MCs. Cysts were exclusively located in the inner nuclear layer in 60% of cases. Mean best-corrected visual acuity in the MC group was lower than that of the non-MC group (P = 0.012). Macular cyst area negatively correlated with best-corrected visual acuity (P = 0.0201). Density of superficial capillary plexus was higher in the MC group (P < 0.0001), whereas area of superficial foveal avascular zone was lower (P < 0.0001). Macular cyst area negatively correlated with density of deep capillary plexus (P < 0.001). CONCLUSION: The incidence of INL-MCs after silicone oil removal is high. These are associated with impaired vision and macular vascular remodeling. We highlight their similarity with the "retrograde maculopathy" phenomenon.

Evolution of Dome-shaped Macula Is Due to Differential Elongation of the Eye Predominant in the Peri-dome Region.

PURPOSE: To determine the mechanism behind macular bulge height increase in eyes with dome-shaped macula (DSM). DESIGN: Retrospective, observational case series. METHODS: Eyes presenting with DSM followed up for a minimum of 1 year were examined using ocular biometry and spectral-domain optical coherence tomography at baseline and at end of follow-up. Axial length (AL), DSM bulge height, and central and peripheral choroidal thickness (nasal, temporal, superior, and inferior quadrants) were reported. Eyes were categorized into 2 groups for comparison: the "mini-DSM" group (DSM < 100 µm) and the "classic" DSM group (DSM > 100 µm). RESULTS: Fifty-eight eyes (33 patients) were studied: 32 (55%) were classic DSM and 26 (45%) mini-DSM. During the mean follow-up of 51.76 ± 36.01 months, mean AL increased from 26.99 ± 2.94 mm to 27.12 ± 3.09 mm (P = .010) and mean macular bulge height increased from 235.88 ± 282.47 µm to 262.34 ± 317.15 µm (P < .001). DSM height change was significantly higher than AL change (P < .001). Mean peripheral choroidal thickness significantly decreased nasally (P = .008), temporally (P = .026), and inferiorly (P < .001). Mini-DSM eyes exhibited shorter AL (26.17 vs 27.66 mm; P = .027), greater visual acuity (0.169 vs 0.437 logMAR; P = .002), and fewer macular complications compared to classic DSM eyes. CONCLUSIONS: Macular bulge increase in DSM is associated with eye elongation and overall thinning of the peripheral choroid. DSM might result from differential elongation of the eye predominant in the peri-dome region. Mini-DSM (ie, inferior to 100 µm) are characterized by slower evolution, better visual prognosis, and fewer complications compared to "classic" DSM.

A new visual acuity test on touchpad for vision screening in children.

AIM: To validate a visual acuity (VA) test application on touchpad in the screening of pediatric population by comparing VA results obtained with conventional tests. METHODS: A cohort of 101 patients, 44 girls and 57 boys with a median of 6.5 years old (3-10 years of age), presenting for eye examinations in Ophthalmology Department (Strasbourg, France) between November 1st, 2018, and February 1st, 2019 were enrolled. Monocular and binocular VA testing was performed on the subject using both a standard test and the touchpad application (Monoyer, "E" or, Pigassou depending of children's capacities). Patients were excluded if they were physically or mentally unable to use the touchpad. The duration of each tests, the painfulness, the comprehension, the attention of children during the test and test's preferences were also evaluated. RESULTS: There was a good linear correlation and intra-class correlation coefficient [ICC=0.50 (0.34, 0.64) for binocular acuity, 0.74 (0.64, 0.82) for right eyes and 0.525 (0.37, 0.66) for left eye]. The standard errors of measurement were very low (0.08, 0.05, 0.08 for binocular VA, right eyes VA and left eyes VA, respectively). There was no difference between two tests for right eye (P=0.126), left eye (P=0.098) and binocular acuity (P=0.085). Non inferiority was proved for all binocular [-0.06 (-0.09, -0.03)], right eye [-0.04 (-0.07, -0.01)] and left eye [-0.06 (-0.09, -0.02)] VA. The sensitivity and specificity, which correspond to the ability for our app to detect amblyopia, were 92% and 80% respectively. CONCLUSION: Our touchpad application represents an efficient and valid test of VA in children with a high specificity to detect visual impairment.

Proteasome subunit PSMC3 variants cause neurosensory syndrome combining deafness and cataract due to proteotoxic stress.

The ubiquitin-proteasome system degrades ubiquitin-modified proteins to maintain protein homeostasis and to control signalling. Whole-genome sequencing of patients with severe deafness and early-onset cataracts as part of a neurological, sensorial and cutaneous novel syndrome identified a unique deep intronic homozygous variant in the PSMC3 gene, encoding the proteasome ATPase subunit Rpt5, which lead to the transcription of a cryptic exon. The proteasome content and activity in patient's fibroblasts was however unaffected. Nevertheless, patient's cells exhibited impaired protein homeostasis characterized by accumulation of ubiquitinated proteins suggesting severe proteotoxic stress. Indeed, the TCF11/Nrf1 transcriptional pathway allowing proteasome recovery after proteasome inhibition is permanently activated in the patient's fibroblasts. Upon chemical proteasome inhibition, this pathway was however impaired in patient's cells, which were unable to compensate for proteotoxic stress although a higher proteasome content and activity. Zebrafish modelling for knockout in PSMC3 remarkably reproduced the human phenotype with inner ear development anomalies as well as cataracts, suggesting that Rpt5 plays a major role in inner ear, lens and central nervous system development.

Serous Retinal Detachment in Dome-Shaped Macula Is Associated with Greater Central Choroidal Blood Flow Measured by Optical Coherence Tomography Angiography.

PURPOSE: Dome-shaped macula (DSM) is characterized by an inward bulge in the macula, often associated with a myopic staphyloma. One complication of DSM is particularly studied: foveolar serous retinal detachment (SRD). This study analyzed the variations of optical coherence tomography angiography (OCT-A) decorrelation signal in cases of DSM with and without SRD. METHODS: This was a retrospective study including twenty height eyes presenting with DSM. OCT-A scans were recorded, and the intensity of the choroidal decorrelation signal was quantified to analyze choroidal blood flow (CBF) in central, temporal, and nasal macular areas. The size of retinal pigment epithelium (RPE) atrophy was evaluated. RESULTS: CBF in the central area was significantly greater in the SRD group than in the no-SRD group (7.00 × 105 vs. 2.58 × 105) (p = 0.0049). CBF appeared decreased in the subfoveal area compared with the periphery for patients without SRD (p = 0.0107). The size of RPE atrophy was 0.762 optic disc area ±0.87. RPE atrophy correlated very significantly with CBF (p = 0.0012). CONCLUSION: A greater retrofoveolar CBF intensity is associated with the presence of SRD. These changes could reflect variations of CBF, and may represent a potential explanation for the pathogenesis of SRD in DSM.

Robot-Assisted Simulated Strabismus Surgery.

PURPOSE: This study aims to investigate the feasibility of robot-assisted simulated strabismus surgery using the new da Vinci Xi Surgical System and to report what we believe is the first use of a surgical robot in experimental eye muscle surgery. METHODS: Robot-assisted strabismus surgeries were performed on a strabismus eye model using the robotic da Vinci Xi Surgical System. On the lateral rectus of each eye, we performed a procedure including, successively, a 4-mm plication followed by a 4-mm recession of the muscle to end with a 4-mm resection. Operative time from conjunctival opening to closing and successful completion of the different steps with or without complications or unexpected events were assessed. RESULTS: Robot-assisted strabismus procedures were successfully performed on six eyes. The feasibility of robot-assisted simulated strabismus surgery is confirmed. The da Vinci Xi system provided the appropriate dexterity and operative field visualization necessary to perform conjunctival and Tenon's capsule opening and closing, muscle identification, suturing, desinsertion, sectioning, and resuturing. The mean duration to complete the whole procedure was 27 minutes (range, 22-35). There were no complications or unexpected intraoperative events. CONCLUSIONS: Experimental robot-assisted strabismus surgery is technically feasible using the new robotic da Vinci Xi Surgical System. This is, to our knowledge, the first use of a surgical robot in ocular muscle surgery. TRANSLATIONAL RELEVANCE: Further experimentation will allow the advantages of robot-assisted microsurgery to be identified while underlining the improvements and innovations necessary for clinical use.

Dark adaptation changes in highly myopic patients.

PURPOSE: The objective of this study was to determine whether the dark adaptation time was longer in highly myopic patients than in emmetropic patients and whether there was a correlation between dark adaptation results and axial length. PATIENTS AND METHODS: We conducted a retrospective study that included highly myopic patients with -6.00 dioptres or more, matched to emmetropic control patients of the same age. All patients underwent an automated adaptometry protocol that calculates the rod intercept that reflects rod-mediated dark adaptation. Axial length was measured. Colour photographs were taken to look for retinal atrophic lesions. RESULTS: A total of 25 highly myopic patients and 25 control patients were included. The mean rod intercept was 4.38 (±1.60) min in the myopic patients and 4.27 (±1.41) min in the control patients. This difference was not statistically significant ( p = 0.79). However, in myopic patients, the longer the axial length was, the longer the dark adaptation time was ( p = 0.0003). In addition, dark adaptation was significantly longer in myopic patients with retinal pigment epithelium atrophy than in patients without lesions ( p = 0.0398). CONCLUSION: In this study, dark adaptation time did not significantly differ between myopic patients and controls but was correlated with axial length in patients with severe myopia and was significantly longer in the presence of retinal pigment epithelium atrophic lesions.

Screening for Retinopathy of Prematurity: Insight into Optimizing Screening.

PURPOSE: To determine the factors influencing the time from preterm birth and retinopathy of prematurity (ROP) detection to optimize the timing of the initial screening. METHODS: This multicenter retrospective study enrolled preterm infants born before 32 weeks of gestational age (GA) and/or weighing less than 1,500 g between January 1, 2011, and December 31, 2015. ROP screening was performed using fundus photography with a wide-field camera. Population and follow-up characteristics were recorded. RESULTS: Among the 1,266 preterm infants observed, 795 were retained for analysis. One hundred seventy-four (21.6%) cases of ROP were detected with the first examination performed at 32.3 ± 1.6 weeks of postmenstrual age (PMA) and 5.4 ± 1.0 weeks of postnatal age (PNA). The first signs of ROP were detected at 34.0 ± 1.9 weeks of PMA and 7.2 ± 1.8 weeks of PNA, respectively. In the multivariate analysis, an older GA, a longer duration of mechanical ventilation, and a lower birth weight were correlated with a longer time between preterm birth and ROP detection (p < 0.0001, p < 0.0001, and p = 0.0359, respectively). CONCLUSION: The first examination for ROP screening should be individualized to fit the first screening examination as closely as possible to the first signs of ROP in order to avoid unnecessary examinations without missing ROP.

Epiretinal Membrane in Dome-Shaped Macula Complicated with Serous Retinal Detachment: Transient Efficacy of Surgery.

Dome-shaped macula (DSM) is an entity recently described as a convex anterior protrusion of the macular area within a posterior myopic staphyloma. Specific complications were associated with DSM, like serous retinal detachment (SRD). We describe a woman presenting with a decreased vision at 20/50. SD-OCT scans were performed, showing a macular bulge. SRD was present and an epiretinal membrane could also be observed. Fluorescein angiography and indocyanin green angiography did not show any leakage nor choroidal neovascularization. Epiretinal membrane peeling was performed, and 3 months after surgery, SRD completely disappeared. However, SRD reappeared 1 year after surgery and enlarged within 2 years following surgery. In conclusion, two mechanisms could be considered for physiopathology of SRD: first, the epiretinal membrane may have exerted traction on the macular retina, second, vitreous body might constitute a tank for cytokines and/or other factors, triggering subretinal fluid accumulation, leading to SRD.

Choroidal Thickness and Ametropia in Children: A Longitudinal Study.

PURPOSE: To determine the relationship of subfoveal choroidal thickness (ChT), refraction, and axial length in children, and evaluate the evolution of subfoveal ChT with time in myopic versus nonmyopic eyes. METHODS: A total of 229 eyes of 115 children aged 2 to 16 years were included in the study. Refraction under cycloplegia, axial length, and subfoveal ChT were measured at baseline with comparative investigations at 15 months follow-up. RESULTS: The probability for the subfoveal ChT to be thinner in myopic children compared to nonmyopic children was 0.9999. We found a relation between subfoveal ChT and axial length. At 15 months follow-up, subfoveal ChT was found to have increased in the nonmyopic eyes, but decreased in myopic patients. CONCLUSIONS: A number of studies have already shown the choroid to play an important role in the process of emmetropization. We found that ChT had a different evolution in myopic children compared to nonmyopic children. A thinner choroid may predict the onset, or progression, of myopia. Further studies, with longer follow-up, are necessary to confirm this hypothesis.