Swept-source optical coherence tomography angiography findings in a case of primary vitreoretinal lymphoma over a three-year follow-up.

BACKGROUND: Vitreoretinal lymphoma (VRL) still represents a diagnostic challenge for retinal specialists. Early diagnosis and treatment are critical for a better prognosis. Several diagnostic tools have proven helpful in the identification of VRL abnormalities. However, swept-source OCT angiography (SS-OCT-A) findings and their long-term follow-up are yet to be explored. CASE PRESENTATION: a 42-year-old man presented with blurred vision in his left eye for 2 weeks. He denied any systemic symptoms. A multimodal imaging examination was performed, raising the clinical suspicion of VRL and guiding the ensuing diagnostic procedures. The patient underwent treatment and at the last FU visit three years later, no disease signs were present on fundus examination, nor on oncologic evaluation. Some novel SS-OCT-A features were identified, and uncommonly reported findings were examined over a long-term follow-up. At baseline multiple hyperreflective alterations were detected on the enface outer retina slabs and choriocapillary analysis revealed low reflectance areas in the foveal and parafoveal areas. One month after the first presentation, multiple hyperreflective retinal lesions in a vertical shape were detected on OCT which appeared on midretinal slabs of enface SS-OCT-A as hyperreflective spots mainly located near second-order retinal vessels. These alterations remarkably reduced after treatment. CONCLUSION: SS-OCT-A may be a useful imaging technique in the detection of VRL, providing ophthalmologists additional findings that assist the diagnosis and follow-up of this disease. This may prove useful for a more timely and precise diagnosis, prompt therapy, and treatment response monitoring. The original aspects found in this case may provide grounds for future studies, ultimately fostering a better understanding of the disease.

Fovea-sparing internal limiting membrane peeling with inverted flap technique versus standard internal limiting membrane peeling for symptomatic myopic foveoschisis.

To study the long-term outcomes of standard ILM peeling and fovea sparing with inverted flap (FSIF) peeling for symptomatic myopic foveoschisis (MF). This retrospective observational study included 36 eyes of 34 consecutive patients who underwent vitrectomy with standard ILM peeling and FSIF peeling for MF between April 2012 and march 2020. The primary outcome measures included best-corrected visual acuity (BCVA) and central foveal thickness (CFT) at 1 month and final visit and postoperative development of macular hole. There were 14 eyes in the standard ILM peeling group and 22 eyes and in the FSIF peeling groups with a mean FU of 34.2 months (SD 23.3; min. 12-max. 96) and 27.7 months (SD 14.9; min. 12-max. 63), respectively. In both groups BCVA was not significantly improved at 1 month but improved at last visit from 0.55 ± 0.21 to 0.37 ± 0.29 in the standard ILM peeling group (P = 0.0154) and from 0.57 ± 0.27 to 0.28 ± 0.23 in the FSIF peeling group (P < 0.0001). At 1 month and final visit CMT decreased from 572 ± 183.5 µm to 277.5 ± 95.2 µm and to 250.4 ± 96.1 µm, respectively, in the standard ILM peeling group and from 589.9 ± 189.8 µm to 383 ± 110.1 µm and 162.3 ± 74.8 µm in the FSIF peeling group (P < 0.001 for both groups at both time-points). The preoperative and postoperative BCVA and CMT showed no significant differences between groups. Three of the eyes in the standard ILM peeling group developed postoperative macular hole at 1, 10, 24 months, respectively, and none of the eyes in the FSIF peeling group. Multivariate analysis revealed that a better BCVA was the only independent factor correlated with the final BCVA. In this study, standard ILM peeling and FSIF peeling were both beneficial in improving the anatomy and function of eyes with MF. Postoperative MH may occur up to 2 years after standard peeling and seem effectively prevented by FSIF peeling.

Use of Heavy Silicon Oil as Intraocular Tamponade for Inferior Retinal Detachment Complicated by Proliferative Vitreoretinopathy: A Multicentric Experience.

INTRODUCTION: This is a multicentric study on the use of heavy silicon oil (HSO) as an intraocular tamponade for inferior retinal detachment (RD) complicated by proliferative vitreoretinopathy (PVR). METHODS: 139 eyes treated for RD with PVR were included in the study. 10 (7.2%) were affected by primary RD with inferior PVR, while 129 (92.8%) were affected by recurrent RD with inferior PVR. 102 eyes (73.9%) had received a silicon oil (SO) tamponade in a previous intervention prior to receiving HSO. Mean follow-up was 36.5 (standard deviation = 32.3) months. RESULTS: The median interval between HSO injection and removal was 4 months (interquartile range: 3). At the time of HSO removal, the retina was attached in 120 eyes (87.6%), whereas in 17 eyes (12.4%), it had re-detached while the HSO was in situ. 32 eyes (23.2%) showed recurrent RD. A subsequent RD relapse was observed in 14.2% of cases with no RD at the time of HSO removal, and in 88.2% if an RD was present at the time of HSO removal. Advancing age showed a positive association with retinal attachment at the end of follow-up, while the risk of RD relapse at the end of the follow-up showed a significant negative association with HSO tamponade duration and with the use of SO rather than air or gas as post-HSO tamponade materials. Mean best corrected visual acuity was 1.1 logarithm of minimum angle of resolution at all follow-up time points. 56 cases (40.3%) needed treatment for elevated intraocular pressure (IOP), with which no clinically relevant variables were associated during follow-up. CONCLUSION: HSO represents a safe and effective tamponade in cases of inferior RD with PVR. The presence of RD at the time of HSO removal is a negative prognostic factor for the development of a subsequent RD relapse. According to our findings, in cases of RD at the time of HSO removal, a short-term tamponade should definitely be avoided, in favor of SO. Special attention must be paid to the risk of IOP elevation, and patients should be closely monitored.

Lamellar macular defects: are degenerative lamellar macular holes truly degenerative?

Purpose: To investigate morpho-functional changes after surgical treatment for ERM foveoschisis or lamellar macular hole (LMH), and to evaluate whether the two entities are associated with different healing processes and long-term outcomes. Design: Retrospective interventional case series. Methods: A total of 56 eyes, treated for lamellar macular defects and followed up for 24 months, were enrolled. The eyes were divided into two groups: 34 with ERM foveoschisis and 22 with LMH. Changes in the following features were evaluated and compared between the two groups: best-corrected visual acuity (BCVA), external limiting membrane (ELM) and ellipsoid zone (EZ) defects, central foveal thickness (CFT), and autofluorescence (FAF) diameter and area. Results: After surgery, progressive BCVA improvement was observed with no significant difference between the two groups (p-value: 0.06). An increased number of eyes with intact outer-retinal layers was found both in the ERM foveoschisis and LMH groups. FAF diameter and area decreased significantly throughout the FU with no significant difference between the two groups (p-value: 0.2). Conclusion: In the present study, significant functional and microstructural improvements were observed after surgery for both ERM foveoschisis and LMH, demonstrating considerable repair potential in both types of lamellar defects. These findings question the true "degenerative" nature of LMH.

Intravitreal Brolucizumab for Neovascular Age-Related Macular Degeneration in a Vitrectomized Eye.

The efficacy of intravitreal anti-VEGF may be reduced in vitrectomized eyes due to accelerated drug clearance. Given its longer durability, brolucizumab may represent a suitable therapeutic option. However, its efficacy in vitrectomized eyes remains to be explored. Herein, we describe the management of a macular neovascularization (MNV) in a vitrectomized eye with brolucizumab after unsuccessful treatment with other anti-VEGF. A 68-year-old male was treated with pars plana vitrectomy for epiretinal membrane in his left eye (LE) in 2018. After surgery, best corrected visual acuity (BCVA) improved to 20/20 with a remarkable reduction of metamorphopsia. After 3 years, the patient returned, presenting visual loss in the LE due to MNV. He was treated with intravitreal bevacizumab injections. However, after the loading phase, an increased lesion size and exudation with worsening BCVA were detected. Therefore, the treatment was switched to aflibercept. However, after three monthly intravitreal injections, further worsening was recorded. Treatment was then switched to brolucizumab. Anatomical and functional improvement was noticed 1 month after the first brolucizumab injection. Two additional injections were performed, and further improvement was recorded with BCVA recovery to 20/20. At the last follow-up visit 2 months after the third injection, no recurrence was detected. In conclusion, determining whether anti-VEGF injections are efficacious for vitrectomized eyes would be helpful for ophthalmologists managing such patients, as well as when considering pars plana vitrectomy in eyes at risk of MNV. In our case, brolucizumab was found to be effective after unsuccessful treatment with other anti-VEGF. Additional studies are required to evaluate the safety and efficacy of brolucizumab for MNV in vitrectomized eyes.

SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS IN A CASE OF PACHYCHOROID NEOVASCULOPATHY IN RETINITIS PIGMENTOSA.

PURPOSE: To report a rare case of pachychoroid neovasculopathy in retinitis pigmentosa (RP) and to describe its features and changes after treatment with bevacizumab as documented by swept-source optical coherence angiography. METHODS: A case report of a 69-year-old man with a history of RP who presented at our clinic with an acute decrease in visual acuity (Best corrected visual acuity) in his left eye. RESULTS: Upon the first examination, best-corrected visual acuity in the left eye was 20/50. Fundus examination and fundus autofluorescence showed bilaterally typical features of RP, and enhanced depth imaging-optical coherence tomography revealed a pachychoroid pattern. Fluorescein angiography and indocyanine green angiography suggested the presence of a choroidal neovascularization in the left eye, although no clear evidence of any neovascular network could be identified. Swept-source optical coherence angiography was performed, confirming the presence of a choroidal neovascularization network. The patient was treated with 2 monthly intravitreal injections of bevacizumab. After treatment, BVCA improved to 20/25, and no evidence of the vascular network was detectable on swept-source optical coherence angiography. CONCLUSION: Our case reports the uncommon association of RP with pachychoroid neovasculopathy. Swept-source optical coherence angiography proved to be a useful imaging technique for the diagnosis and follow-up of this condition. Intravitreal bevacizumab represents an effective treatment for choroidal neovascularization associated with RP.

Temporal variation of optical coherence tomography biomarkers as predictors of anti-VEGF treatment outcomes in diabetic macular edema.

PURPOSE: To report a longitudinal analysis of specific optical coherence tomography (OCT) features in eyes with diabetic macular edema (DME) treated with anti-VEGF. METHODS: A total of 133 eyes of 103 consecutive patients with center-involving DME were included in the study. The eyes were treated between August 2008 and April 2019 with three monthly intravitreal anti-VEGF injections, either with or without prompt or deferred laser, followed by pro re nata (PRN) re-treatment. The following OCT biomarkers were evaluated: subfoveal neuroretinal detachment (SND) (defined as present (SND+) or absent (SND-)), hyperreflective retinal foci (HRF) number (defined as: absent/few(HRF-) or moderate/many (HRF+)), external limiting membrane (ELM) integrity, central macular thickness (CMT), and central retinal thickness (CRT). Changes in SND status and in the number of HRF were evaluated at each DME recurrence throughout the follow-up(FU) period. Mutual correlation among OCT biomarkers and their relationship with visual and anatomic outcomes were assessed both at baseline and over the FU period. RESULTS: The mean FU was 71.2 months (SD 28.4; min. 12-max. 111). At baseline, the prevalence of SRD+ was 27.8% and a high number of HRF were detected in 41.4% of the eyes. A significant reduction in the number of HRF, CMT, CRT, and in the prevalence of SND was recorded in the post-loading phase (p-value <0.0001). In DME recurrences, the presence of SND+ and HRF+ was significantly more frequent in eyes with baseline SND+ and HRF+ compared to eyes presenting baseline SND- and HRF- (p-value <0.0001). No role of SND (p-value: 0.926) and HRF (p-value: 0.281) as baseline predictors of visual and anatomic outcomes was demonstrated, while a worse visual outcome was significantly correlated with a higher incidence of relapsing SND+ (p-value <0.0001) and HRF+ (p-value <0.0028) throughout the FU period. CONCLUSION: In this study, SND and HRF were frequently present in DME recurrences with the same pattern exhibited at baseline, suggesting that these OCT biomarkers may characterize a specific pattern of DME that repeats over time. Moreover, the results suggested that the persistence and recurrence of SND and HRF may account for a decrease in visual function more than the baseline prevalence of these biomarkers. Further studies are required to confirm these findings.

Microstructural Macular Changes after Pars Plana Vitrectomy for Primary Rhegmatogenous Retinal Detachment.

PURPOSE: This study aimed to describe foveal microstructural changes after pars plana vitrectomy (PPV) with air tamponade for rhegmatogenous retinal detachment (RRD). METHODS: External limiting membrane (ELM) and ellipsoid zone (EZ) integrity, cystoid macular edema (CME), and subretinal fluid bleb (SB) development were analyzed using optical coherence tomography in 59 eyes over a 6-month follow-up period after PPV surgery for RRD. Eyes were grouped as macula-on (n = 30) or macula-off (n = 29), and the association between ELM and EZ recovery and best-corrected visual acuity (BCVA) was investigated. Predictive factors for ELM and EZ recovery were also identified. RESULTS: The interval between symptom onset and surgery did not significantly differ between the macula-on and macula-off groups. Macula-on patients showed ELM and EZ integrity throughout, whereas macula-off patients had ELM and EZ integrity restored in 89.7% and 86.2% cases, respectively, with a resultant increase in final BCVA. Significant associations were found between preoperative macular involvement and ELM/EZ restoration. ELM/EZ recovery was also inversely associated with CME development. Significant associations were also found between final BCVA and preoperative BCVA and EZ recovery. CME and SB development were equally distributed between the 2 groups. CONCLUSION: Prompt surgery for macula-off RRD allows the progressive recovery of outer retinal layers and significant visual gain.

The prevalence of vitreomacular adhesion in eyes with macular oedema secondary to retinal vein occlusion selected for intravitreal injections.

PURPOSE: To assess the prevalence of vitreomacular adhesion (VMA) in consecutive naïve eyes diagnosed with macular oedema (ME) secondary to retinal vein occlusion (RVO) and to longitudinally evaluate the incidence of vitreomacular interface changes over time and the influence on response to treatment. DESIGN: Retrospective cross-sectional analysis and longitudinal cohort study conducted at two Italian tertiary referral centres. METHODS: A total of 295 eyes, treated with intravitreal ranibizumab and/or dexamethasone for ME secondary to RVO between June 2008 and May 2018, were enrolled in the study. 280 fellow eyes met the inclusion criteria and were included as control group. The vitreomacular interface status was evaluated by spectral domain optical coherence tomography (OCT) and graded according to the OCT-based International Classification System developed by the International Vitreomacular Traction Study (IVTS) group. RESULTS: At baseline, VMA was present in 130 (44.07%) RVO eyes and 142 (50.7%) control eyes (no statistically significant difference was found; p = 0.455). Mean follow-up (FU) was 35.98 months (min 6 - max 112). Throughout the FU, the incidence of spontaneous release of VMA (RVMA) in RVO eyes was significantly higher in comparison with that of the control group [59 (41.84%) RVO eyes versus 18 (12.33%) control eyes; p < 0.0001]. The number of injections in VMA+ eyes was significantly higher when compared with VMA- eyes. No significant difference was found between VMA+ and VMA- eyes regarding their mean best-corrected visual acuity (BCVA) at baseline and at each annual time point (p = 0.2). Differences in central macular thickness (CMT) were significant only at the baseline evaluation (p = 0.0303). CONCLUSIONS: Vitreomacular adhesion (VMA) was not found to be more prevalent in eyes with RVO compared to healthy fellow eyes, and RVO, in turn, did not result in a higher persistence of VMA over time. This suggests that VMA and RVO might be two independent retinal phenomena, with no mutual pathogenetic influence. Vitreomacular adhesion (VMA) might have an impact on the response to treatment, since it was found to result in a more intensive treatment regimen; however, it did not affect visual and anatomic outcomes. These results do not support vitrectomy or PVD induction in the prevention, nor the treatment, of RVO.

Retrobulbar triamcinolone for inflammatory choroidal neovascularization in pregnancy.

BACKGROUND: Choroidal neovascularization (CNV) in pregnancy has rarely been described. A differential diagnosis between inflammatory, idiopathic, and myopic CNV may be challenging. Moreover, there is no consensus on management, and therapeutic options may be further limited by patient and physician concerns about potential risk to the fetus. Herein, we report a case of inflammatory CNV during pregnancy and describe a previously unreported management approach with retrobulbar triamcinolone injections. CASE PRESENTATION: A 36-year-old woman presented with vision loss and metamorphopsia in her right eye while 21 weeks pregnant. She was diagnosed with an inflammatory CNV based on the following multimodal imaging findings: a type 2 lesion with the "pitchfork sign" on OCT, along with the absence of tomographic signs of myopic CNV, and the presence on autofluorescence of multiple hyper-autofluorescent spots, interpreted as focal areas of inflammation at the level of the outer retina and inner choroid. The patient refused oral corticosteroids and any intravitreal injection therapies. Therefore, she was treated with two trans-Tenon's retrobulbar injections of triamcinolone acetonide after explaining the procedure and acquiring consent. The treatment resulted in a regression of inflammatory signs and a reduction of neovascular activity. No adverse events occurred for the mother or the baby, neither during the pregnancy nor after delivery. CONCLUSION: Inflammatory CNV may be rarely associated with pregnancy. The correct diagnosis is crucial to allow the consideration of all possible management options. To the best of our knowledge, this is the first reported case of treatment with retrobulbar triamcinolone injections. This may represent a suitable therapeutic option in the absence of any other therapeutic approaches.

Scleral thinning surgery for bullous retinal detachment with retinal pigment epithelial tear in central serous chorioretinopathy: a case report.

BACKGROUND: Bullous serous retinal detachment (RD) with retinal pigment epithelial (RPE) tear is a rare and severe variant of chronic central serous chorioretinopathy (CSC). Due to its atypical presentation, it may raise diagnostic issues, leading to inappropriate therapeutic procedures. The optimum treatment for this CSC variant is still uncertain. CASE PRESENTATION: A 65-year-old male was referred for vitreo-retinal surgery with a provisional diagnosis of rhegmatogenous RD in his right eye. Dilated fundus examination showed an inferior bullous RD with no evidence of retinal breaks, while a large RPE tear was detected in the temporal quadrant. Ocular ultrasound showed no mass lesion. The axial length was 23.63 mm. Enhanced depth imaging optical coherence tomography (EDI-OCT) revealed a pachychoroid pattern in both eyes. The patient referred a history of CSC in the right eye and the recent use of intravenous corticosteroids for bronchitis. Laser therapy and photodynamic therapy were not applicable due to the extension and elevation of the RD. Two months after oral treatment with eplerenone, the subretinal fluid increased significantly. The patient underwent two 4 × 4 mm deep lamellar sclerectomies in the inferior quadrants. The surgical treatment resulted in complete RD resolution. CONCLUSION: A correct diagnosis of bullous variant of chronic CSC with RPE tear is critical to avoid inappropriate procedures and to prevent severe visual loss as a result of neuroretinal damage. Scleral thinning surgery may be considered a valid option, resulting in rapid and long-lasting resolution of RD.

Intravitreal Injections for Macular Edema Secondary to Retinal Vein Occlusion: Long-Term Functional and Anatomic Outcomes.

PURPOSE: To report the long-term visual and anatomic outcomes of intravitreal injections for macular edema (ME) secondary to retinal vein occlusion (RVO) in a real-life clinical setting. DESIGN: Retrospective interventional case series. METHODS: A total of 223 consecutive eyes with ME secondary to RVO, treated with the first three intravitreal Ranibizumab or dexamethasone injections between August 2008 and September 2018, were enrolled in the study. Subsequent retreatment was guided by best-corrected visual acuity (BCVA) and central macular thickness (CMT) measurements, aimed at achieving macular fluid regression and BCVA stability. BCVA and CMT were recorded at baseline and at subsequent annual time points. The mean number of injections administered each year and the incidence of adverse events were recorded. RESULTS: The mean BCVA and CMT at baseline were 0.79 logMar (SD 0.71) and 615.7 µm (SD 257.5), respectively. The mean follow-up (FU) period was 47.8 months (min 12-max 120). At 12 months, the mean BCVA and CMT had significantly improved to 0.62 logMar (SD 0.68; p < 0.0001) and 401.04 µm (SD 257.5), respectively. The mean follow-up (FU) period was 47.8 months (min 12-max 120). At 12 months, the mean BCVA and CMT had significantly improved to 0.62 logMar (SD 0.68; p < 0.0001) and 401.04 . CONCLUSION: Intravitreal Ranibizumab and/or dexamethasone injections were found to be effective at inducing a long-lasting improvement of BCVA and CMT in a real-life clinical setting. A safety profile similar to that already well-established in Ranibizumab and dexamethasone treatment was observed, as well as a steady decrease in the number of intraocular injections required. The results support intravitreal treatments for BRVO and CRVO in patient populations with similar characteristics in similar settings.

Large Idiopathic Macular Hole Surgery: Remodelling of Outer Retinal Layers after Traditional Internal Limiting Membrane Peeling or Inverted Flap Technique.

OBJECTIVE: To investigate the influence of the inverted flap technique compared with traditional internal limiting membrane (ILM) peeling in the postoperative remodelling of outer retinal layers of idiopathic macular holes (MHs) >450 µm. METHODS: We analyzed medical records and imaging studies of all patients with an idiopathic MH >450 µm who underwent vitrectomy at the Sacco University Hospital, Milan, and the Sacro Cuore Don Calabria Hospital, Verona, Italy, between January 2008 and December 2017. Out of 41 eyes evaluated, 17 were treated with traditional ILM peeling and 24 with the inverted ILM flap technique. All patients underwent follow-up examinations every 3 months and all of them completed a final visit 12 months after surgery. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters were evaluated at each visit. The main outcome measures were the postoperative recovery rate of the external limiting membrane (ELM) and ellipsoid zone (EZ), and postoperative BCVA. Correlations between OCT measurements and visual outcome were analyzed. RESULTS: The ELM recovery rate in the ILM peeling group (15/17 eyes, 88%) was higher than in the ILM flap group (14/24 eyes, 58%) (p = 0.079). The EZ recovery rate was similar in the 2 groups, 7/17 eyes (41%) in the ILM peeling and 8/24 eyes (33%) in the ILM flap group (p = 0.744). Eyes without a persistent hyper-reflective "plug" at the edges of the MH showed a significantly higher EZ recovery rate (11/18, 61%) compared with eyes showing a persistent plug (4/23, 17%) (p = 0.008). The mean BCVA improved significantly in both groups: from 0.93 logMAR (20/170) to 0.26 logMAR (20/36) in the ILM peeling and from 0.98 logMAR (20/190) to 0.37 logMAR (20/46) in the ILM flap group. The final BCVA tended to be better in the ILM peeling group (p = 0.085). CONCLUSIONS: Given the limited information about the influence of ILM flap versus traditional ILM peeling in the postoperative remodelling of large idiopathic MHs, our data provides some new insights into the healing process of MHs >450 µm. This should be considered as part of the decision process about whether to perform an ILM flap in these patients.

Intravitreal Recombinant Tissue Plasminogen Activator and Sulphur Hexafluoride Gas for Submacular Haemorrhage Displacement in Age-Related Macular Degeneration: Looking behind the Blood.

PURPOSE: To evaluate the effectiveness of recombinant tissue plasminogen activator (rtPA) and sulphur hexafluoride gas (SF6) intravitreal injection for the displacement of large submacular haemorrhages (SMH) secondary to neovascular age-related macular degeneration and for guiding the selection of additional treatments or observations for choroidal neovascularization (CNV). METHODS: The medical records of consecutive patients with recent-onset, large SMH, treated at Sacro Cuore Hospital from January 2004 to May 2016, were retrospectively analysed. All eyes underwent a 0.05-mL intravitreal injection of 50 µg rtPA, 0.3 mL of 100% SF6, and then face-down positioning. Afterwards, the eyes received additional treatments for CNV or observation, based on the severity and extent of the underlying pathology. The multimodal imaging features revealed after blood displacement were analysed and then correlated to the treatment selected as a second therapeutic option. RESULTS: A total of 96 eyes met the inclusion criteria and was evaluated in this study. SMH was displaced from the fovea in the majority of the eyes (76%), allowing several diagnostic tools to evaluate the underlying macular features. In 19 cases (19.8%) exhibiting severe macular damage, no additional treatment was applied. In the remaining eyes, subsequent treatments included anti-vascular endothelial growth factor injections (44.8%), photodynamic therapy (n = 2), and submacular surgery (35.4%). Statistically significant correlations were found between the macular findings revealed after blood displacement and the additional treatments or observations selected for the underlying disease. The mean follow-up was 35 months. Improvements in visual acuity were statistically significant up to 3 years. CONCLUSION: Intravitreal rtPA and gas injection was found to be effective for the displacement of large SMH, allowing postoperative diagnostic testing, and thus guiding the opportunity to apply further treatments. The addition of subsequent individualized treatments may allow long-term visual gain in selected cases.

Pathogenicity of new BEST1 variants identified in Italian patients with best vitelliform macular dystrophy assessed by computational structural biology.

BACKGROUND: Best vitelliform macular dystrophy (BVMD) is an autosomal dominant macular degeneration. The typical central yellowish yolk-like lesion usually appears in childhood and gradually worsens. Most cases are caused by variants in the BEST1 gene which encodes bestrophin-1, an integral membrane protein found primarily in the retinal pigment epithelium. METHODS: Here we describe the spectrum of BEST1 variants identified in a cohort of 57 Italian patients analyzed by Sanger sequencing. In 13 cases, the study also included segregation analysis in affected and unaffected relatives. We used molecular mechanics to calculate two quantitative parameters related to calcium-activated chloride channel (CaCC composed of 5 BEST1 subunits) stability and calcium-dependent activation and related them to the potential pathogenicity of individual missense variants detected in the probands. RESULTS: Thirty-six out of 57 probands (63% positivity) and 16 out of 18 relatives proved positive to genetic testing. Family study confirmed the variable penetrance and expressivity of the disease. Six of the 27 genetic variants discovered were novel: p.(Val9Gly), p.(Ser108Arg), p.(Asn179Asp), p.(Trp182Arg), p.(Glu292Gln) and p.(Asn296Lys). All BEST1 variants were assessed in silico for potential pathogenicity. Our computational structural biology approach based on 3D model structure of the CaCC showed that individual amino acid replacements may affect channel shape, stability, activation, gating, selectivity and throughput, and possibly also other features, depending on where the individual mutated amino acid residues are located in the tertiary structure of BEST1. Statistically significant correlations between mean logMAR best-corrected visual acuity (BCVA), age and modulus of computed BEST1 dimerization energies, which reflect variations in the in CaCC stability due to amino acid changes, permitted us to assess the pathogenicity of individual BEST1 variants. CONCLUSIONS: Using this computational approach, we designed a method for estimating BCVA progression in patients with BEST1 variants.

Inverted ILM Flap for the Treatment of Myopic Macular Holes: Healing Processes and Morphological Changes in Comparison with Complete ILM Removal.

PURPOSE: To investigate the microstructural changes after successful myopic macular hole (MMH) surgery, comparing inverted ILM flap and complete ILM removal techniques, and their association with visual function. METHODS: Spectral-domain optical coherence tomography (SD-OCT) was used to evaluate both external limiting membrane (ELM) and ellipsoid zone (EZ) recovery in 40 eyes of 39 patients who underwent pars plana vitrectomy with either inverted internal limiting membrane flap technique (n=27) or complete ILM removal (n=13) to achieve MH closure. The association between ELM and EZ recovery and visual acuity was also investigated. The patients were followed up at 1 year. RESULTS: ELM and EZ was recovered in 72% and 62% of cases, respectively, regardless of the surgical techniques 1 year after surgery. A strong positive association between the ELM and EZ recovery and the mean BCVA was found: regardless of the surgical technique, this was statistically significant at each time point (p < 0.05). None of the baseline variables were found to act as predictive factors for either ELM or EZ. CONCLUSION: The inverted ILM flap technique did not affect the MMH healing processes compared to complete ILM removal. Thus, the presence of the ILM plug did not interfere with the restoration of both ELM and EZ, which correlated with functional recovery.