AFG3L2 and ACO2-Linked Dominant Optic Atrophy: Genotype-Phenotype Characterization Compared to OPA1 Patients.

PURPOSE: Heterozygous mutations in the AFG3L2 gene (encoding a mitochondrial protease indirectly reflecting on OPA1 cleavage) and ACO2 gene (encoding the mitochondrial enzyme aconitase) are associated with isolated forms of Dominant Optic Atrophy (DOA). We aimed at describing their neuro-ophthalmological phenotype as compared with classic OPA1-related DOA. DESIGN: Cross-sectional study. METHODS: The following neuro-ophthalmological parameters were collected: logMAR visual acuity (VA), color vision, mean deviation and foveal threshold at visual fields, average and sectorial retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL) thickness on optical coherence tomography. ACO2 and AFG3L2 patients were compared with an age- and sex-matched group of OPA1 patients with a 1:2 ratio. All eyes were analyzed using a clustered Wilcoxon rank sum test with the Rosner-Glynn-Lee method. RESULTS: A total of 44 eyes from 23 ACO2 patients and 26 eyes from 13 AFG3L2 patients were compared with 143 eyes from 72 OPA1 patients. All cases presented with bilateral temporal-predominant optic atrophy with various degree of visual impairment. Comparison between AFG3L2 and OPA1 failed to reveal any significant difference. ACO2 patients compared to both AFG3L2 and OPA1 presented overall higher values of nasal RNFL thickness (P = .029, P = .023), average thickness (P = .012, P = .0007), and sectorial GCL thickness. These results were confirmed also comparing separately affected and subclinical patients. CONCLUSIONS: Clinically, DOA remains a fairly homogeneous entity despite the growing genetic heterogeneity. ACO2 seems to be associated with an overall better preservation of retinal ganglion cells, probably depending on the different pathogenic mechanism involving mtDNA maintenance, as opposed to AFG3L2, which is involved in OPA1 processing and is virtually indistinguishable from classic OPA1-DOA.

SURGICAL APPROACH FOR SUBFOVEAL DENSIRON 68 BUBBLE REMOVAL IN A CASE OF RECURRENT INFERIOR RETINAL DETACHMENT.

PURPOSE: To describe a surgical approach to remove a retained subfoveal Densiron 68 bubble in a case of recurrent inferior retinal detachment. METHODS: A 23-gauge pars plana vitrectomy was performed to remove the subfoveal silicone oil bubble and to treat the retinal detachment. Through a midperipheral retinal tear, we reached the subfoveal space by extending the retinal detachment up to the macular region. We inserted in the subretinal space a Charles cannula protected with a silicone tip to catch and aspirate the bubble. Intraoperative optical coherence tomography successfully guided the surgical maneuvers. RESULTS: We achieved the complete removal of the bubble from the subretinal space, and this led to the restoration of the retinal morphology with functional improvement, although the fovea developed atrophy. CONCLUSION: We reported a surgical approach for the removal of a retained subfoveal Densiron 68 bubble that combines a macular detachment together with the aspiration of the bubble using a protected Charles cannula. This technique may provide an alternative approach in the management of this challenging complication.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS BEFORE AND AFTER VITRECTOMY FOR MACULAR HOLES: Useful or Useless?

PURPOSE: To investigate the vascular remodeling of optical coherence tomography angiography in full-thickness macular hole surgery. METHODS: This retrospective, observational case series included 33 eyes of 33 patients with a full-thickness macular hole who underwent epiretinal membrane removal. Data were collected on best-corrected visual acuity, structural B-scan optical coherence tomography, and optical coherence tomography angiography preoperatively and at 1, 3, and 6 months postoperatively. Optical coherence tomography angiography was used to assess the retinal vascular density (VD) of the superficial vascular plexus and deep vascular plexus (DVP). Vascular density was assessed using the Early Treatment Diabetic Retinopathy Study grid for the whole, inner, and outer grids. RESULTS: A statistically significant correlation was found between the VD (whole, inner, and outer grids) of the superficial vascular plexus alone from baseline to 1-month postoperatively (P < 0.001). Similarly, VD was correlated from baseline to 1, 3, and 6 months postoperatively to the whole (P < 0.0005, F = 23.22), inner (P < 0.0005, F = 28.23), and outer Early Treatment Diabetic Retinopathy Study grids of DVP (P = 0.033, F = 3.49). The best-corrected visual acuity and VD were significantly correlated with the superficial vascular plexus and DVP at baseline and 6 months (P < 0.05, all correlations). The most significant correlation was observed at 6 months between best-corrected visual acuity and DVP in the whole, inner, and outer Early Treatment Diabetic Retinopathy Study grids (P < 0.001). CONCLUSION: Superficial vascular plexus and DVP are affected by full-thickness macular holes, with the most significant effects being on the DVP. Full-thickness macular hole surgery leads to an improvement in the best-corrected visual acuity in many eyes and the restoration of the VD, especially of the DVP.

The Role of OCT Angiography in the Assessment of Epiretinal Macular Membrane.

BACKGROUND: The aim of this observational study is to assess pre- and postoperative retinochoroidal vascular changes in patients undergoing epiretinal macular membrane (ERM) surgery by using optical coherence tomography angiography (OCTA). MATERIALS AND METHODS: 23 eyes affected by ERM and those which underwent phacovitrectomy associated with ERM peeling were enrolled. They were evaluated using structural OCT and OCTA before surgery and at 1, 3, and 6 months postoperatively. RESULTS: We found a statistically significant (p < 0.05) increase in the superficial capillary plexus vessel density (VD) from baseline to the 6-month follow-up. We observed a large increase in both the perfusion density (PD) and the VD of the deep capillary plexus between baseline and the 6-month follow-up (p < 0.001). A significant decrease in the VD and PD of the choriocapillaris (CC) from baseline to the 1st month and a significant increase in CC perfusion density at the 6-month follow-up compared to the preoperative value were revealed. The FAZ area and perimeter after surgery significantly increased during the follow-up (p < 0.001) at baseline retinal and choroidal plexi with a lower PD or VD correlated with worse visual acuity (p < 0.05 for all plexi). At baseline and at the 1-month follow-up, a significant correlation was found with the FAZ area and the FAZ perimeter: a smaller FAZ area or a smaller FAZ perimeter was correlated to a lower visual acuity. Before surgery, negative correlations (p < 0.05) were found between the Govetto ERM stages and perfusion density of the SCP and the DCP and between the Govetto stages and vessel density of the DCP. CONCLUSIONS: In our study, OCTA detected vascular alterations induced by the presence of the ERM, allowing several correlations with functional data. In these patients, OCTA may be useful to add new potential surgical prognostic factors.

Optical Coherence Tomography Angiography for the Evaluation of Retinal Vasculature in Fabry Disease: Our Experience and Review of Current Knowledge.

Purpose: Optical coherence tomography angiography (OCTA) is a non-invasive and objective tool for the evaluation of the retinal microvascular changes in Fabry disease (FD). We investigated changes in retinal vasculature in FD patients, and the possible correlation with systemic parameters, by using OCTA, and reviewed the current status of literature. Methods: Thirteen FD patients (eight females, five males, mean age 49.85 ± 14.7 years) were compared with 13 age- and sex-matched healthy controls. OCTA 3 × 3 mm macular scans were performed in all subjects. We evaluated the vessel density and vessel perfusion in distinct macular areas (whole, inner, and outer) of both the superficial capillary plexus (SCP VD and SCP VP) and of the deep capillary plexus (DCP VD and DCP VP). We also evaluated the foveal avascular zone (FAZ) metrics (area, perimeter, and circularity), and correlation between systemic and OCTA parameters. A literature review on the current understanding of OCTA in FD is then presented. Results: FD patients showed significantly lower SCP VD values in the whole area (17.37 ± 2.08 mm-1 vs. 18.54 ± 1.21 mm-1; p-value 0.022), as well as in the outer area (17.46 ± 2.10 mm-1 vs. 19.08 ± 1.14 mm-1; p-value 0.002), but not in the inner. Even the DCP VD was significantly lower in all the imaged areas: whole (17.75 ± 3.93 mm-1 vs. 19.71 ± 1.20 mm-1; p-value 0.024), outer (18.25 ± 4.17 mm-1 vs. 20.33 ± 1.20 mm-1; p-value 0.023), and inner (19.54 ± 4.17 mm-1 vs. 21.96 ± 1.55 mm-1; p-value 0.011). There were no significant differences in vessel perfusion parameters (both SCP VP and DCP VP ones) and FAZ. No significant correlations were found between the OCTA parameters and systemic parameters (maximal left ventricular wall thickness and glomerular filtration rate) in FD patients. Conclusions: OCTA can be considered as a promising non-invasive tool, which enables a quantitative evaluation of retinal vascular involvement in FD, despite the varying data reported in literature. Our results support the use of OCTA as an objective tool to evaluate retinal vascular abnormalities in FD. The utility of OCTA in FD needs to be validated by longitudinal studies taking into account the overall progression of the disease.

Combining cataract surgery with 25-gauge high-speed pars plana vitrectomy: A prospective study.

PURPOSE: To compare visual outcome and postoperative complications of combined 25-gauge pars plana vitrectomy and phacoemulsification with vitrectomy alone surgery in patients with epiretinal membrane and macular hole. METHODS: A total of 110 eyes (73 eyes with epiretinal membrane and 37 eyes with macular hole) were enrolled in this prospective study. The eyes were divided into two groups: Group A included 55 eyes which underwent phacovitrectomy at the same time and Group B included 55 eyes which underwent vitrectomy alone. Follow-up visits were at 1, 3, and 6 months. RESULTS: The best-corrected visual acuity correlation by analysis of variance measurement showed statistically non-significant differences between the two groups (p = 0.32). The post hoc analysis from baseline, 1°, 2°, and 3° follow-ups was not statistically significant (p > 0.05). The most common postoperative complication was cystoid macular edema that has been detected in 11 patients (10%) (seven eyes in Group A and four eyes in Group B): 2 patients (1.8%) developed a chronic macular edema. Intraocular hypertension occurred in five eyes (4.5%) (three in Group A and two in Group B). Four eyes (3.6%) underwent another surgical procedure for a persistent macular hole (two in Group A and two in Group B). The intraocular lens repositioning was performed one day after surgery in three eyes (2.7%) (Group A). The mean preoperative visual acuity was not different between the two groups (p = 0.80). CONCLUSION: No significative differences between combined surgery and vitrectomy alone have been detected, in terms of postoperative complications and visual outcome.

Computer-assisted retinal vessel diameter evaluation in Fabry disease.

PURPOSE: Fabry disease retinal vascular involvement has been widely reported, with narrowing of the retinal arterioles, dilation and irregularity of the retinal veins, and exaggerated tortuosity of the retinal vessels. We evaluated retinal vessel diameter in Fabry disease, by means of a dedicated software, aiming to provide a quantitative marker of retinal vascular network abnormalities in Fabry disease patients. MATERIAL AND METHODS: Observational case-control study evaluating different branches of vessels, peripapillary vessels (group A), temporal vascular arcades (group B), and second-order collaterals of the temporal arcades (group C). We obtained the vessel diameters values from eye fundus digital images of eight Fabry disease patients and eight age-sex matched controls, using a semiautomatic software. Mann-Whitney test was used to compare the Fabry disease group versus the control group. RESULTS: The difference between the average diameters of all the types of vessels considered were significantly smaller in Fabry disease patients compared to healthy controls, resulting in a decrease in size (mm) of 10.9% for group A, 7.8% for group B, and 7.4% for group C. The most evident difference between Fabry disease patients and controls was found in the largest vessels. CONCLUSION: A computer-assisted analysis of retinal vessel diameter in Fabry disease by means of dedicated software showed narrower retinal arteries in Fabry disease patients than in controls. Our data support the use of semiautomatic assessment of retinal vessel attenuation as an objective and reproducible method to evaluate retinal vascular alterations in Fabry disease, providing a clinical non-invasive tool for early diagnosis and disease monitoring.

OCT Angiography Findings in Macula-ON and Macula-OFF Rhegmatogenous Retinal Detachment: A Prospective Study.

Background: The aim of the study was to evaluate pre-operative and post-operative retinal vasculature using optical coherence tomography angiography (OCTA) in patients who underwent rhegmatogenous retinal detachment (RRD) surgery repair. Materials and Methods: A total of 33 eyes were included in this prospective consecutive observational study: 15 affected by macula-ON and 18 by macula-OFF RRD. Superficial (SCP), deep capillary plexus (DCP), and foveal avascular zone (FAZ) area variations were evaluated by OCTA and correlated with visual acuity (VA) during a six-month follow-up. Results: In the macula-ON group, the preoperative vascular density (VD) of the whole SCP (wSCP) on affected eyes was lower than that of the fellow eyes (p < 0.05); this difference disappeared at 6 months after surgery (p = 0.88). The wSCP VD and the parafoveal SCP (pfSCP) VD increased during follow-up (p < 0.05); moreover, the higher the preoperative wSCP and pfSCP VD, the better the baseline VA (p < 0.05). In the macula-OFF group, at the first and sixth months after surgery, the larger the FAZ, the lower the VA (p < 0.05). Conclusions: Macula-ON SCP VD affected preoperative VA, and it was lower than the fellow eye, but recovered over time. In the macula-OFF group, a larger FAZ area was related to a worse VA, as is the case in diabetes and in retinal vein occlusion (RVO).

The COVID-19 Pandemic from an Ophthalmologist's Perspective.

The current coronavirus disease 2019 (COVID-19) pandemic is rapidly spreading around the world. The first doctor to report this new disease was an ophthalmologist: this exemplifies the role of ophthalmologists in an infectious disease pandemic. Here we review how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the eye and discuss implications for ophthalmologists.

Morpho-Functional Evaluation of Full-Thickness Macular Holes by the Integration of Optical Coherence Tomography Angiography and Microperimetry.

(1) Objective: To use optical coherence tomography angiography (OCTA) and microperimetry (MP) to evaluate the correlation between retinal structure and function in patients with idiopathic, full-thickness macular holes (FTMHs) (2) Methods: This prospective, observational study included 11 eyes of 10 patients with FTMHs evaluated before surgery using OCTA and MP. MP sensitivity maps were superimposed and registered on slabs corresponding to superficial capillary plexus (SCP) and deep capillary plexus (DCP) on OCTA, and on the outer plexiform layer (OPL) and the Henle fiber layer (HFL) complex in en face OCT. On these maps, mean retinal sensitivity was calculated at 2° and 4°, all centered on the FTMH. Cystic cavity extension was assessed on the slab corresponding to the OPL + HFL complex in en face OCT and DCP in OCTA using the Image J software (Version 1.49v; National Institutes of Health, Bethesda, MD, USA); (3) Results: Absolute scotomas were observed corresponding to the FTMH. Additionally, rings of relative scotoma in the perilesional area were detected and correlated to the cystic spaces on en face OCT and OCTA. There was a significant correlation between reduced retinal sensitivity at 2° and 4° diameters around the FTMH and the extension of cystic areas (p < 0.01). There was a significant correlation between the extension of cystic cavities and BCVA (p < 0.01). (4) Conclusions: Morpho-functional analysis of FTMH using OCTA and MP, and the correlation between vascular abnormalities and impaired retinal sensitivity, may provide new, useful information. This integrated evaluation of FTMH may be useful to determine the function-structure correlation before and after vitreoretinal surgery, in order to gain a better understanding of the functional consequences induced by the morphological alterations, assessing outcomes in a more objective way, and potentially adding new surgical prognostic factors.

IN VIVO OBSERVATION OF RETINAL VASCULAR DEPOSITS USING ADAPTIVE OPTICS IMAGING IN FABRY DISEASE.

PURPOSE: To report a novel finding in patients with Fabry disease, that is, the observation by adaptive optics ophthalmoscopy of intracellular lipidic deposits in retinal vessels. METHODS: Observational two-center case series. Eighteen patients with genetically proven Fabry disease underwent flood-illumination adaptive optics ophthalmoscopy imaging (rtx1; Imagine Eyes, Orsay, France) of retinal vessels. RESULTS: Fourteen patients (78% of all patients; 7 of the 10 women and 7 of the 8 men) showed paravascular punctuate or linear opacities in both eyes. In the least-affected patients, these were seen only in the wall of precapillary arterioles as discrete spots of 5 µm to 10 µm large, whereas in those more severely affected, capillaries and first-order vessels were also involved with diffuse opacification of the wall. These deposits sometime showed a striated pattern, suggesting colocalization with vascular smooth muscle cells. CONCLUSION: Adaptive optics ophthalmoscopy of retinal vessels may be of interest for patients with Fabry disease, providing noninvasive, gradable evaluation of microvascular involvement.

Quantitative Analysis of Conjunctival and Retinal Vessels in Fabry Disease.

Fabry Disease (FD) is a rare X-linked lysosomal storage disorder characterized by systemic and ocular involvement. It has been described an increasing in retinal and conjunctival vessel tortuosity and this feature represents an important marker for the disease. Currently, there is not an objective method to measure and quantify this parameter. We tested a new semi-automatic software measuring retinal and conjunctival vessel tortuosity from eye fundus and conjunctival digital images in a group of FD patients. We performed an observational case-control study evaluating three mathematical parameters describing tortuosity (sum of angle metric [SOAM], product of angle distance [PAD], triangular index [I2e]) obtained from fundus and conjunctival pictures of 11 FD patients and 11 age and sex-matched controls. Both eyes were considered. Mann-Whitney test was used to compare the FD group versus the control group and, within the FD group, male versus female patients. Linear regression analysis was performed to evaluate the possible association of retinal and conjunctival vessels tortuosity parameters with age and with specific markers of systemic disease's progression. The tortuosity parameters (SOAM, PAD and I2e) were significantly higher in retinal vessels and in conjunctival nasal vessels in FD patients in comparison with the controls (p=0.003, p=0.002, p=0.001 respectively for retina) (p=0.023, p=0.014, p=0.001 respectively for nasal conjunctiva). No significant association was found between retinal and conjunctival tortuosity parameters and increasing age or systemic involvement markers. Vessel tortuosity represents an important clinical manifestation in FD. A computer-assisted analysis of retinal and conjunctival vasculature demonstrated an increased vessels tortuosity in patients affected by Fabry disease. This non-invasive technique might be useful to help the diagnosis in early stages, to establish disease severity and monitor its progression.

EDI OCT evaluation of choroidal thickness in Stargardt disease.

PURPOSE: Choroidal thickness (CT) evaluation with EDI-OCT in Stargardt Disease (STGD), considering its possible association with some clinical features of the disease. METHODS: CT was evaluated in 41 STGD patients and in 70 controls. Measurements were performed in the subfoveal position and at 1000 µm nasally and temporally. CT average values in STGD and in the control group were first compared by means of Student's T test. Then, the possible association between CT and some clinical features was evaluated by means of linear regression analysis. Considered clinical parameters were: age, age on onset, duration of the disease, visual acuity, foveal thickness, Fishman clinical phenotype, visual field loss and ERG response. RESULTS: Average CT was not significantly different between controls and STGD patients. In the STGD group the correlation between CT and age (r = 0.22, p = 0.033) and age of onset (r = 0.05, p = 0.424) was modest, while that of CT with disease duration (r = 0.30, p<0.001) was moderate. CT and foveal thickness were also significantly but modestly correlated (r = 0.15, p = 0.033). CONCLUSION: In our series average CT is not significantly changed in STGD in comparison with the controls. Nevertheless a choroidal thinning may be identified in the more advanced stages of the disease.

EDI-OCT evaluation of choroidal thickness in retinitis pigmentosa.

PURPOSE: To evaluate choroidal thickness (CT) in retinitis pigmentosa (RP) using enhanced depth imaging (EDI) optical coherence tomography (OCT). METHODS: A retrospective analysis of a group of patients with RP who underwent EDI-OCT was performed. Choroidal thickness measurements were compared with those of age- and sex-matched healthy subjects. In the RP group, the possible association between subfoveal CT and some clinical parameters (visual acuity, age, age at disease onset, duration of the disease, macular thickness, visual field loss, electroretinography [ERG]) was evaluated. RESULTS: The study recruited 39 patients with RP with an average age of 43.3 ± 11.3 years while the control group consisted of 73 healthy subjects with an average age of 42.9 ± 12.10 years. On average, CT was significantly thinner in the RP group compared to the controls (p<0.0001). In the RP group, we could not find any significant association between CT and the considered clinical parameters even if there was a trend for decreasing CT with increasing age (r = -0.23, p = 0.096). In the control group, subfoveal CT showed a slightly significant correlation with age (r = -0.21, p = 0.04) but not with macular thickness and visual acuity. CONCLUSIONS: In our series, CT was significantly lower in the RP group in comparison with the controls, as measured by EDI-OCT, but did not correlate with age, age at onset, duration of the disease, macular thickness, visual acuity, visual field loss, or ERG responses. Although the clinical implications of choroidal changes in RP have not yet been clearly determined, the evaluation of choroidal features may provide information that could be useful to clarify the pathophysiology of the disease.

Morphologic study of the cornea by in vivo confocal microscopy and optical coherence tomography after bifocal refractive corneal inlay implantation.

PURPOSE: To evaluate the biocompatibility of the Flexivue Microlens intracorneal inlay based on healing of corneal wounds and analysis of corneal structural features using in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT). SETTING: Ophthalmology Department, Misericordia e Dolce Hospital, Prato, Italy. DESIGN: Case series. METHODS: The intracorneal inlay was inserted in a stromal pocket created in the nondominant eye of emmetropic presbyopic patients using a femtosecond laser. In vivo confocal microscopy and AS-OCT examinations were performed preoperatively and 1, 6, and 12 months postoperatively. RESULTS: The mean follow-up was 7.6 months. In the early postoperative period, IVCM showed intense cellular activity in the stroma around the inlay, edema, inflammation, and degenerative material deposition but normal regularity after 12 months. Anterior segment OCT showed a regular planar shape of the corneal pocket in all eyes. The mean of the side-cut angles was 30.7 degrees. The mean difference between the measured and planned pocket depth was 9.77 µm. At 1 month, hyperreflective areas beneath the inlay and microfolds were observed in 21 of the 52 eyes. After 12 months, the anterior segment profile was regular and interface pocket reflectivity decreased over time. Six patients had inlay removal postoperatively (3 before 6 months; 3 before 12 months); after removal, IVCM and AS-OCT showed clear corneas without signs of irregularity. CONCLUSION: In vivo confocal microscopy and AS-OCT analysis showed that the inlay elicited a low-level wound-healing response in its immediate vicinity with no alteration in the corneal structures. FINANCIAL DISCLOSURE: Dr. M. Fantozzi is a member of the Presbia medical advisory board. No other author has a financial or proprietary interest in any material or method mentioned.

Improving Boston type 1 keratoprosthesis procedure: one-touch femtosecond-assisted preparation and centration of donor carrier tissue.

PURPOSE: We describe a technique to avoid decentration of the visual axis of the Boston type 1 keratoprosthesis (Kpro), performing 2 concentric trephinations with femtosecond laser. METHODS: Two concentric side cuts were performed in a donor cornea using the 150-kHz Intralase FS laser. Within the same applanation procedure, an 8.5-mm-diameter anterior side cut was performed, followed by a concentric 3-mm-diameter anterior side cut. RESULTS: The technique was successfully replicated in 7 cases. CONCLUSIONS: Femtosecond laser-assisted double trephination results in a correctly prepared donor cornea, and in an inner side precisely matched with the prosthesis. At the end of the surgery, the Kpro was correctly centered.