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.

The p-ERG spatial acuity in the biomedical pig under physiological conditions.

Pigs are becoming an important pre-clinical animal species for translational ophthalmology, due to similarities with humans in anatomical and physiological patterns. Different models of eye disorders have been proposed, and they are good candidates to assess biocompatibility/functionality of retinal prostheses. Electroretinography is a common tool allowing to gain information on retinal function, with several types of electroretinogram (ERG) been implemented including full field (ff-ERG), multifocal (mf-ERG) and pattern (p-ERG). p-ERG represents a valuable tool to monitor Retinal Ganglion Cells (RGCs) activity and can be used to calculate p-ERG spatial acuity. Unfortunately, scarce methodological data are available regarding recording/interpretation of p-ERG and retinal acuity in biomedical pigs yet enhancing knowledge regarding pig vision physiology will allow for more refined and responsible use of such species. Aim of this study was to record p-ERG in juvenile pigs to functionally assess visual acuity. Six female hybrid pigs underwent two p-ERG recording sessions at 16 and 19 weeks of age. Photopic ff-ERG were also recorded; optical coherence tomography (OCT) and histology were used to confirm retinal integrity. ff-ERG signals were repeatable within/across sessions. All p-ERG traces consistently displayed characterizing peaks, and the progressive decrease of amplitude in response to the increment of spatial frequency revealed the reliability of the method. Mean p-ERG spatial acuities were 5.7 ± 0.14 (16 weeks) and 6.2 ± 0.15 cpd (19 weeks). Overall, the p-ERG recordings described in the present work seem reliable and repeatable, and may represent an important tool when it comes to vision assessment in pigs.

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.

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.

Biocompatibility of a Conjugated Polymer Retinal Prosthesis in the Domestic Pig.

The progressive degeneration of retinal photoreceptors is one of the most significant causes of blindness in humans. Conjugated polymers represent an attractive solution to the field of retinal prostheses, and a multi-layer fully organic prosthesis implanted subretinally in dystrophic Royal College of Surgeons (RCS) rats was able to rescue visual functions. As a step toward human translation, we report here the fabrication and in vivo testing of a similar device engineered to adapt to the human-like size of the eye of the domestic pig, an excellent animal paradigm to test therapeutic strategies for photoreceptors degeneration. The active conjugated polymers were layered onto two distinct passive substrates, namely electro-spun silk fibroin (ESF) and polyethylene terephthalate (PET). Naive pigs were implanted subretinally with the active device in one eye, while the contralateral eye was sham implanted with substrate only. Retinal morphology and functionality were assessed before and after surgery by means of in vivo optical coherence tomography and full-field electroretinogram (ff-ERG) analysis. After the sacrifice, the retina morphology and inflammatory markers were analyzed by immunohistochemistry of the excised retinas. Surprisingly, ESF-based prostheses caused a proliferative vitreoretinopathy with disappearance of the ff-ERG b-wave in the implanted eyes. In contrast, PET-based active devices did not evoke significant inflammatory responses. As expected, the subretinal implantation of both PET only and the PET-based prosthesis locally decreased the thickness of the outer nuclear layer due to local photoreceptor loss. However, while the implantation of the PET only substrate decreased the ff-ERG b-wave amplitude with respect to the pre-implant ERG, the eyes implanted with the active device fully preserved the ERG responses, indicating an active compensation of the surgery-induced photoreceptor loss. Our findings highlight the possibility of developing a new generation of conjugated polymer/PET-based prosthetic devices that are highly biocompatible and potentially suitable for subretinal implantation in patients suffering from degenerative blindness.

Subretinally injected semiconducting polymer nanoparticles rescue vision in a rat model of retinal dystrophy.

Inherited retinal dystrophies and late-stage age-related macular degeneration, for which treatments remain limited, are among the most prevalent causes of legal blindness. Retinal prostheses have been developed to stimulate the inner retinal network; however, lack of sensitivity and resolution, and the need for wiring or external cameras, have limited their application. Here we show that conjugated polymer nanoparticles (P3HT NPs) mediate light-evoked stimulation of retinal neurons and persistently rescue visual functions when subretinally injected in a rat model of retinitis pigmentosa. P3HT NPs spread out over the entire subretinal space and promote light-dependent activation of spared inner retinal neurons, recovering subcortical, cortical and behavioural visual responses in the absence of trophic effects or retinal inflammation. By conferring sustained light sensitivity to degenerate retinas after a single injection, and with the potential for high spatial resolution, P3HT NPs provide a new avenue in retinal prosthetics with potential applications not only in retinitis pigmentosa, but also in age-related macular degeneration.

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.

The porcine iodoacetic acid model of retinal degeneration: Morpho-functional characterization of the visual system.

Porcine models of ophthalmological diseases are often used in pre-clinical translational studies due to pigs' similarities to humans. In particular, the iodoacetic acid (IAA) model of photoreceptor degeneration seems to mimic well the endstage phenotype of human pathologies as retinitis pigmentosa and age-related macular degeneration, with high potential for prosthesis/retinal devices testing. IAA is capable of inducing photoreceptor death by blockage of glycolysis, and its effects on the retina have been described. Nonetheless, up to date, literature lacks of a comprehensive morpho-functional characterization of the entire visual system of this model. This gap is particularly critical for prosthesis testing as inner retinal structures and optic pathways must be preserved to elicit cortical responses and restore vision. In this study, we investigated the functional and anatomical features of the visual system of IAA-treated pigs and compared them to control animals. IAA was administered intravenously at 12 mg/kg; control animals received saline solution (NaCl 0.9% w/v). Electrophysiological analyses included full-field (ffERGs) and pattern (PERGs) electroretinograms and flash visually evoked potentials (fVEPs). Histological evaluations were performed on the retina and the optic pathways and included thickness of the different retinal layers, ganglion cells count, and immunohistochemistry for microglial cells, macroglial cells, and oligodendrocytes. The histological results indicate that IAA treatment does not affect the morphology of the inner retina and optic pathways. Electrophysiology confirms the selective rod and partial cone degeneration, but is ambiguous as to the functionality of the optic pathways, seemingly preserved as indicated by the still detectable fVEPs. Overall, the work ameliorates the characterization of such rapid and cost-effective model, providing more strength and reliability for future pre-clinical translational trials.

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.

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.

New Insights Into the Development and Progression of Geographic Atrophy After Full Thickness Autologous Choroidal Graft.

Purpose: To investigate if the contiguity between native and transplanted retinal pigment epithelium (RPE) represents a protective factor against the progression of atrophy after autologous choroidal graft. In addition, the changes in fundus autofluorescence (FAF) in the contiguous and noncontiguous RPE areas were explored. Methods: The first postoperative reliable FAF image was selected and divided into sectors based on the characteristics of the RPE at the edge of the graft. The sectors were categorized into three groups: contiguous RPE, noncontiguous RPE, and not classifiable. The area of RPE atrophy, inside and outside the graft, was measured for each sector at baseline, one, three, and five years of follow-up. The FAF pattern outside the graft was evaluated for every sector at baseline and during the follow-up. Results: Nineteen patients met the inclusion criteria and were included in this study. Trend analysis showed that the atrophy progression outside the graft was statistically significant in areas where native and transplanted RPE were noncontiguous (P < 0.0001) yet not so in contiguous areas (P < 0.058). Inside the graft, both groups showed an increase in atrophy over time. In addition, the noncontiguous group developed more severe increased FAF patterns compared with the contiguous group. Conclusions: RPE contiguity after autologous choroidal graft seems to be a protective factor against atrophy progression, whereas any area of damaged or absent RPE tends to enlarge over time. This may suggest that the transplantation of an RPE sheet is more likely to be effective than an RPE cell suspension.