Prevalence of vitreoschisis-induced vitreous cortex remnants over the peripheral retinal surface in eyes undergoing vitrectomy for primary rhegmatogenous retinal detachment.

PURPOSE: Unremoved vitreoschisis-induced vitreous cortex remnants over the peripheral retinal surface posterior to the vitreous base (pVCR) may increase the risk of surgical failure after primary rhegmatogenous retinal detachment (RRD) repair. The purpose of this study was to validate our previous findings on pVCR prevalence during vitrectomy for RRD and to examine their association with proliferative vitreoretinopathy (PVR) and surgical failure. METHODS: Prospective observational multisurgeon study of 100 eyes of 100 consecutive patients who underwent vitrectomy for RRD by one of four vitreoretinal surgeons. Collected data included detected pVCR and known PVR risk factors. Pooled analysis with our previous retrospective study (251 eyes of 251 patients) was also performed. RESULTS: Initial PVR (≥C) was present and removed in 6/100 (6%) patients, pVCR were detected in 36/100 (36%) patients, pVCR were removed in 30/36 (83%) patients with pVCR, and 4/36 (11%) patients with pVCR were high myopes (≤-6D). Six per cent (6/100) developed a retinal redetachment, of which 3/6 (50%) had initial PVR (≥C). Surgical failure rates in eyes with and without pVCR were 17% (6/36) and 0% (0/64), respectively. In eyes with pVCR and surgical failure, pVCR were not or not completely removed during the first surgery. Overall analysis showed that pVCR were statistically significantly associated with PVR. CONCLUSIONS: This study confirms our previous findings: a pVCR prevalence of around 35% and an association between pVCR, PVR formation and surgical failure in patients undergoing vitrectomy for RRD. More research is needed to determine which patients would benefit most from pVCR removal.

Retinal damage extends beyond the border of the detached retina in fovea-on retinal detachment.

PURPOSE: The aim of this study was to investigate the preoperative and postoperative change in retinal sensitivity in relation to the distance to the retinal detachment (RD) in patients with fovea-on RD. METHODS: We prospectively evaluated 13 patients with fovea-on RD and a healthy control eye. Preoperatively, OCT scans of the RD border and the macula were obtained. The RD border was highlighted on the SLO image. Microperimetry was used to assess the retinal sensitivity at the macula, the RD border and the retina around the RD border. At 6 weeks, 3 and 6 months postoperatively, follow-up examinations of OCT and microperimetry were performed in the study eye. Microperimetry was performed once in control eyes. Microperimetry data were overlaid on the SLO image. The shortest distance to the RD border was calculated for each sensitivity measurement. The change in retinal sensitivity was calculated as control-study. The relation between the change in retinal sensitivity and the distance to the RD border was assessed using a locally weighted scatterplot smoothing curve. RESULTS: Preoperatively, the greatest loss in retinal sensitivity was 21 dB at 3° inside the RD which decreased linearly, through the RD border, and reached a plateau of 2 dB at 4°. For 6 weeks and 3 months postoperatively, the greatest retinal sensitivity loss remained at 3° inside the RD but was 4 dB and sensitivity loss decreased linearly to a plateau of 0 dB at 5° outside the RD. At 6 months postoperatively, the greatest sensitivity loss was 2 dB at 3° inside the RD, and decreased linearly to a plateau of 0 dB at 2° outside the RD. CONCLUSIONS: Retinal damage extends beyond the detached retina. Retinal sensitivity loss of the attached retina decreased drastically as the distance to the RD increased. Postoperative recovery occurred for both attached and detached retina.

Randomised controlled trial on robot-assisted versus manual surgery for pucker peeling.

BACKGROUND: The aim was to explore the feasibility and safety of performing common surgical steps in epiretinal membrane (ERM) peeling using the Preceyes Surgical System (PSS). METHODS: In a tertiary centre, 15 pseudophakic patients with an idiopathic ERM were randomised to robot-assistance or manual surgery in a 2:1 ratio. In the robot-assisted group, the following steps were performed using PSS: (1) staining the internal limiting membrane (ILM), (2) removal of the dye, (3) creating an ILM flap, (4) completing the peeling, (5) holding a light pipe and (6) fluid-air exchange. Primary outcome measures were feasibility and safety. Secondary outcome measures were duration, best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Moreover, the distance travelled by the instrument during peeling was assessed using motion tracking software. RESULTS: All steps performed with PSS were feasible with no clinical adverse events or complications. The surgical time was longer in the robot-assisted group (mean 56 min, SD = 12 vs. 24 min, SD = 5). During the study, the duration of robot-assisted surgeries decreased from 72 to 46 min. The distance travelled by the forceps was shorter in the robot-assisted group (mean 403 mm, SD = 186 vs. 550 mm, SD = 134). BCVA and CRT improved equally in both groups. CONCLUSIONS: This is the world's first randomised controlled trial on robotic surgery for ERM. Although more time-consuming, we found that several surgical steps were feasible with assistance of the PSS.

Destructive inflammatory reaction after an autologous retinal pigment epithelium and choroid transplantation: no detection of an auto-immune response.

PURPOSE: Five patients who underwent uncomplicated retinal pigment epithelium (RPE)-choroid transplantation for neovascular age-related macular degeneration developed a destructive inflammatory reaction causing subretinal fluid accumulation and extensive RPE atrophy in the graft. We hypothesized that this inflammation could be caused by an auto-immune response against the graft, resulting in circulating auto-antibodies. The aim of our study was to examine a potential autoimmune origin, which would allow a more targeted therapy approach. METHODS: Five above-mentioned patients and four control groups of five patients each were included: 1) after uncomplicated RPE-choroid transplantation, 2) after full macular translocation, 3) treated with anti-vascular endothelial growth factor, and 4) healthy controls. Histopathology of rejected graft tissue was performed using standard procedures. Presence of RPE-choroid autoantibodies in serum was examined by indirect immunofluorescence and Western blot, and human leukocyte antigen (HLA) typing was performed. RESULTS: Histopathological examination of an explanted graft showed infiltration of T-lymphocytes and macrophages in the choroid and RPE, and an increased number of B-cell lymphocytes were found in the choroid. Indirect immunofluorescence showed weak RPE-choroid autoantibody immunoreactivity in three patients of different groups. Western blot did not show specific RPE-choroid autoantibody immunoreactivity and no difference of HLA genotypes between the groups was found. CONCLUSIONS: Although local mononuclear inflammatory cell infiltration and a high number of B-lymphocytes were observed in an explanted graft, we did not detect serological evidence of an autoimmune origin of the postoperative inflammation using direct immunofluorescence and Western Blot. Alternatively, the graft failure may have been caused by local innate inflammation, triggered by breakdown of tolerance. Based on our current findings of this small study group, we have no rationale to pursue therapies targeted towards autoreactive graft failure. More research is needed to confirm our findings.

Vitrectomy, subretinal Tissue plasminogen activator and Intravitreal Gas for submacular haemorrhage secondary to Exudative Age-Related macular degeneration (TIGER): study protocol for a phase 3, pan-European, two-group, non-commercial, active-control, observer-masked, superiority, randomised controlled surgical trial.

BACKGROUND: Neovascular (wet) age-related macular degeneration (AMD) can be associated with large submacular haemorrhage (SMH). The natural history of SMH is very poor, with typically marked and permanent loss of central vision in the affected eye. Practice surveys indicate varied management approaches including observation, intravitreal anti-vascular endothelial growth factor therapy, intravitreal gas to pneumatically displace SMH, intravitreal alteplase (tissue plasminogen activator, TPA) to dissolve the clot, subretinal TPA via vitrectomy, and varying combinations thereof. No large, published, randomised controlled trials have compared these management options. METHODS: TIGER is a phase 3, pan-European, two-group, active-control, observer-masked, superiority, randomised controlled surgical trial. Eligible participants have large, fovea-involving SMH of no more than 15 days duration due to treatment-naïve or previously treated neovascular AMD, including idiopathic polypoidal choroidal vasculopathy and retinal angiomatous proliferation. A total of 210 participants are randomised in a 1:1 ratio to pars plana vitrectomy, off-label subretinal TPA up to 25 µg in 0.25 ml, intravitreal 20% sulfahexafluoride gas and intravitreal aflibercept, or intravitreal aflibercept monotherapy. Aflibercept 2 mg is administered to both groups monthly for 3 doses, then 2-monthly to month 12. The primary efficacy outcome is the proportion of participants with best-corrected visual acuity (BCVA) gain of ≥ 10 Early Treatment Diabetic Retinopathy (ETDRS) letters in the study eye at month 12. Secondary efficacy outcomes (at 6 and 12 months unless noted otherwise) are proportion of participants with a BCVA gain of ≥ 10 ETDRS letters at 6 months, mean ETDRS BCVA, Radner maximum reading speed, National Eye Institute 25-item Visual Function Questionnaire composite score, EQ-5D-5L with vision bolt-on score, Short Warwick and Edinburgh Mental Wellbeing score, scotoma size on Humphrey field analyser, and presence/absence of subfoveal fibrosis and/or atrophy and area of fibrosis/atrophy using independent reading centre multimodal image analysis (12 months only). Key safety outcomes are adverse events, serious adverse events, and important medical events, coded using the Medical Dictionary for Regulatory Activities Preferred Terms. DISCUSSION: The best management of SMH is unknown. TIGER aims to establish if the benefits of SMH surgery outweigh the risks, relative to aflibercept monotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663750 ; EudraCT: 2020-004917-10.

Validation of a multi-species-specific PCR panel to diagnose patients with suspected postoperative bacterial endophthalmitis.

INTRODUCTION: Currently, patients suspected of endophthalmitis are referred to a tertiary centre for a vitreous biopsy and bacterial culture, thereby causing a treatment delay for the intravitreal antibiotics injection. We developed a new diagnostic tool, multi-mono-PCR (mm-PCR), not requiring viable bacteria, allowing antibiotic injection without delay. Performance of mm-PCR was tested on biopsies from patients with suspected postoperative endophthalmitis with known bacterial culture results. METHODS: Most frequently occurring pathogens in endophthalmitis were determined using published data and treatment logs of endophthalmitis patient of the Rotterdam Eye Hospital. Vitreous biopsies from patients with suspected endophthalmitis were aliquoted in two parts. One part was sent out for bacterial culture and another was stored at -80°C for mm-PCR analysis and, as a backup, also by panbacterial PCR. Twelve vitreous samples from patients not suspected of having endophthalmitis were added as control samples. RESULTS: Concordancy between bacterial culture and mm-PCR was 89% (24 of 27). All twelve control samples were negative. In three nonconcordant samples, the PCR results were most likely the correct ones. CONCLUSION: mm-PCR results are highly concordant with bacterial culture. mm-PCR with panbacterial PCR as backup could be considered a diagnostic tool in patients with endophthalmitis, which would allow us to reverse the order of diagnosis and treatment while maintaining diagnostic surveillance, thereby preventing treatment delay.

Smaller Foveal Avascular Zone in Deep Capillary Plexus Is Associated with Better Visual Acuity in Patients after Macula-off Retinal Detachment Surgery.

Purpose: To associate the change in the foveal avascular zone (FAZ) and vessel density (VD) with final best corrected visual acuity (BCVA) in eyes after macula-off rhegmatogenous retinal detachment surgery, and to investigate the evolution of FAZ and VD during 12 months of follow-up. Methods: We prospectively evaluated 47 patients with macula-off rhegmatogenous retinal detachment and healthy fellow eyes. At 1.5, 3.0, 6.0, and 12.0 months postoperatively, optical coherence tomography angiography scans were obtained from both eyes on a 3.0 × 3.0 mm macula-centered grid. En face images of the superficial vascular plexus, intermediate capillary plexus and deep capillary plexus were used to quantify FAZ and VD. BCVA was assessed with ETDRS-charts (logarithm of the minimal angle of resolution).At 12 months postoperatively, the association between the change in optical coherence tomography angiography parameters and visual function in study eyes was evaluated using the Spearman correlation coefficient. We calculated the BCVA difference and the percentage difference of FAZ and VD between the study and control eye. The evolution of FAZ and VD was investigated with linear mixed-effects models with nested random effects (eyes nested within patients). Results: At 12 months postoperatively, FAZ difference of the deep capillary plexus and BCVA difference were correlated (P = 0.0004, rs = 0.5). Furthermore, there was no evidence that FAZ and VD changed during follow-up. Conclusions: Although FAZ and VD remained stable during 12 months after surgery for macula-off rhegmatogenous retinal detachment, a smaller FAZ in the deep capillary plexus is associated with better BCVA. Translational relevance: Reduction in FAZ area may be caused by angiogenesis to counteract ischemia, therefore therapeutic stimulation of angiogenesis could be beneficial to visual recovery.

Visual Acuity Inadequately Reflects Vision-Related Quality of Life in Patients After Macula-Off Retinal Detachment Surgery.

Purpose: To determine the impact of postoperative visual function on the vision-related quality of life (VRQoL) in patients after anatomically successful surgery for macula-off rhegmatogenous retinal detachment (RRD) and to propose a classification to grade the extent of macular detachment using preoperative optical coherence tomography (OCT) scans. Methods: This prospective study evaluated 48 patients. At 12 months after surgery, visual function assessments were as follows: metamorphopsia (M-CHARTS), aniseikonia (New Aniseikonia Test), best corrected visual acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS]), low contrast BCVA (10% ETDRS), color vision (Hardy Rand Rittler), and stereopsis (Titmus Fly). VRQoL was assessed by the National Eye Institute Visual Functioning Questionnaire-25 (NEIVFQ-25). Associations between visual function parameters and NEIVFQ-25 scores were evaluated. Preoperative OCT-scans were classified into six stages according to the extent of macular detachment based on an ETDRS-grid: incomplete perifoveal detachment (1), incomplete parafoveal detachment (2), incomplete foveal detachment (3), complete foveal detachment (4), complete parafoveal detachment (5), and complete perifoveal detachment (6). Results: General vision and driving were the lowest scoring categories. General vision had the strongest correlation with low contrast BCVA (r = -0.41, P = 0.002), while driving had the strongest correlation with stereopsis (r = -0.39, P = 0.008). All macular detachments were graded stage 3 or beyond. Patients with stage 3 macular detachments had the highest visual function values compared to the other stages. The highest percentage of patients with metamorphopsia, aniseikonia and BCVA>0.1 logMAR was found in stages 5 and 6. Conclusions: Macula-off RRD particularly affects general vision and driving. The extent of macular detachment is a potential predictor for visual function and can be graded using the proposed classification.

PRIMA subretinal wireless photovoltaic microchip implantation in non-human primate and feline models.

PURPOSE: To evaluate the surgical technique for subretinal implantation of two sizes of PRIMA photovoltaic wireless microchip in two animal models, and refine these surgical procedures for human trials. METHODS: Cats and Macaca fascicularis primates with healthy retina underwent vitrectomy surgery and were implanted with subretinal wireless photovoltaic microchip at the macula/central retina. The 1.5mm PRIMA chip was initially studied in feline eyes. PRIMA implant (2mm,1.5mm sizes) arrays were studied in primates. Feasibility of subretinal chip implantation was evaluated with a newly-developed surgical technique, with surgical complications and adverse events recorded. RESULTS: The 1.5mm implant was placed in the central retina of 11 feline eyes, with implantation duration 43-106 days. The 1.5mm implant was correctly positioned into central macula of 11 primate eyes, with follow-up periods of minimum 6 weeks (n = 11), 2 years (n = 2), and one eye for 3 years. One primate eye underwent multi-chip 1.5mm implantation using two 1.5mm chips. The 2mm implant was delivered to 4 primate eyes. Optical coherence tomography confirmed correct surgical placement of photovoltaic arrays in the subretinal space in all 26 eyes. Intraoperative complications in primate eyes included retinal tear, macular hole, retinal detachment, and vitreous hemorrhage that resolved spontaneously. Postoperatively, there was no case of significant ocular inflammation in the 1.5mm implant group. CONCLUSIONS: We report subretinal implantation of 1.5mm and 2mm photovoltaic arrays in the central retina of feline and central macula of primate eyes with a low rate of device-related complications. The in vivo PRIMA implantation technique has been developed and refined for use for a 2mm PRIMA implant in ongoing human trials.

STRICT POSTURING WITH OR WITHOUT BILATERAL PATCHING FOR POSTERIOR VITREOUS DETACHMENT-RELATED VITREOUS HEMORRHAGE.

PURPOSE: To determine whether bilateral patching with posturing is superior to posturing alone in visualizing the superior retina in suspected posterior vitreous detachment (PVD)-related vitreous hemorrhage (VH). METHODS: Prospective randomized controlled trial: 80 patients with fundus-obscuring VH due to suspected retinal tear were randomized to strict posturing and bilateral patching overnight (Treatment A, 40 patients) or posturing (Treatment B, 40 patients). PRIMARY OUTCOME: Visualization of ≥4 clock hours superior retina. SECONDARY OUTCOME MEASURES: laser treatment, vitrectomy rate, and retinal detachment within 12 months. RESULTS: Intention-to-treat analysis: In 38/40 (95%) with Treatment A and 32/40 (80%) with Treatment B, the confirmed diagnosis was PVD-related VH. Visibility of the superior retina for all patients: 29/40 (73%) after Treatment A and 21/40 (53%) after Treatment B (P = 0.07). Subgroup analysis for confirmed PVD-related VH; visibility of the superior retina: 29/38 (76%) after Treatment A and 15/32 (47%) after Treatment B (P = 0.01). In subgroup analysis, vitrectomy rate within 12 months was 61% (Treatment A) and 53% (Treatment B) (P = 0.63). Retinal detachment: eight patients after each treatment. CONCLUSION: In patients with suspected PVD-related VH, overnight bilateral patching was not superior to posturing alone in superior retina visualization, but in a post-hoc analysis of patients with confirmed PVD-related VH, bilateral patching was superior.

PROPHYLACTIC LASER TREATMENT TO DECREASE THE INCIDENCE OF RETINAL DETACHMENT IN FELLOW EYES OF IDIOPATHIC GIANT RETINAL TEARS.

PURPOSE: To evaluate the effectiveness of prophylactic 360° laser treatment in the fellow eye of patients with unilateral idiopathic giant retinal tear (GRT) to prevent the occurrence of a (macula-off) retinal detachment. METHODS: We conducted a retrospective, nonrandomized case-control study. Clinical data of consecutive patients, undergoing surgery for idiopathic GRT, between 2003 and 2015 were analyzed. The data collected included GRT, retinal detachment, and RTs in the fellow eye. RESULTS: We included 129 patients who underwent surgery for an idiopathic GRT, with a mean follow-up period of 107 months. In the observation group, a retinal detachment developed in the fellow eye in 22/51 patients (43.1%), leading to a macula-off detachment in 9/51 patients (17.6%). By contrast, in the prophylactic 360° laser group, only 10/78 (12.8%) patients developed a retinal detachment, leading to a macula-off detachment in 1/78 patient (1.3%). This difference was statistically significant. CONCLUSION: This study suggests that prophylactic 360° laser treatment in the fellow eye of patients with an idiopathic GRT decreased the incidence of retinal detachment, lowering the high risk of visual loss due to a macula-off retinal detachment.

The Influence of Prolongation of Interruptions of Preoperative Posturing and Other Clinical Factors on the Progress of Macula-On Retinal Detachment.

PURPOSE: To evaluate whether prolongation of interruptions of preoperative posturing by sitting upright influences retinal detachment (RD) progression. The secondary objective was to find clinical factors to identify patients with a high risk for RD progression. DESIGN: Prospective cohort study. PARTICIPANTS: One hundred ninety-eight patients divided among 3 cohorts of patients with macula-on RD were included. Inclusion criteria were volume OCT scans of sufficient quality and smallest distance from the fovea to the detachment border of at least 1.25 mm. In the second and third cohort, 50 patients with only superior temporal RD were included. METHODS: Patients were admitted to the ward in anticipation of surgery. Preoperative bed rest and positioning were prescribed. The position of the RD border was determined based on OCT imaging performed at baseline, before and after the usual interruptions for meals or toilet visits. The duration of interruptions was prolonged with sitting upright for 20 minutes in cohort 2 and for 40 minutes in cohort 3. Various secondary outcome measures were defined, such as the baseline area of subretinal fluid (SRF) as measured on ultrasound images in the third cohort. MAIN OUTCOME MEASURES: The RD border displacement was determined. The worst RD progression from baseline was given by the shortest distance to the fovea in any of the OCT scans during follow-up. The worst relative RD progression from baseline was defined as the worst RD progression from baseline as a percentage of the baseline distance between RD border and fovea. RESULTS: The median duration of interruptions was 22, 41, and 58 minutes in cohorts 1, 2, and 3, respectively. The median RD border displacement during interruptions in patients with superior temporal RD was not significantly different among the cohorts (P = 0.28). The correlation coefficient between the SRF area at baseline and worst relative RD progression from baseline was 0.37 (95% confidence interval, 0.04-0.66; P = 0.009). CONCLUSIONS: We did not find a significant increase in RD progression after prolongation of interruptions by sitting upright. Patients with a larger area of SRF on ultrasound showed more RD progression from baseline.

Vitreous Wiping, a new technique for removal of vitreous cortex remnants during vitrectomy.

PURPOSE: Unremoved vitreoschisis-induced vitreous cortex remnants (VCR) are associated with macular pathology. When present on the retinal periphery, they may play a role in proliferative vitreoretinopathy and retinal detachment after vitrectomy. Existing instruments for their removal involve substantial risk of iatrogenic retinal damage. Purpose of this study was to evaluate the use of a new technique, Vitreous Wiping, for removal of VCR during vitrectomy. METHODS: Proof-of-concept case series of six eyes (six patients) treated with vitrectomy for various pathologies (macula-on and macula-off retinal detachment, macular hole, macular pucker and vitreous floaters). Vitreous cortex remnants on the surface of the retina were visualized with triamcinolone and removed by Vitreous Wiping with a rectangular piece of polyvinyl alcohol (PVA) held with intra-ocular forceps. Visual acuity and clinical course were assessed during a follow-up of 6 months. All eyes underwent postoperative macular optical coherence tomography. Eyes without preoperative macular pathology, underwent retinal sensitivity testing and eyes without paracentral pathology underwent visual field analysis. RESULTS: Vitreous cortex remnants could be removed completely in all eyes. There were no intra- or postoperative complications. We observed that PVA is soft like a sponge and vitreous sticks to it, making Vitreous Wiping easier and safer, compared to alternative instruments. Visual acuity improved in all eyes. Microperimetry and visual field analysis revealed no abnormalities related to Vitreous Wiping. CONCLUSION: Vitreoschisis-induced VCR can be removed effectively and safely from the retinal surface by Vitreous Wiping. Larger studies are needed to confirm this promising finding and its potential impact.

Visual acuity of 20/32, 13.5 years after a retinal pigment epithelium and choroid graft transplantation.

PURPOSE: To present the 13.5-year-survival of an autologous retinal pigment epithelium (RPE) and choroid graft transplantation with good visual acuity results. OBSERVATIONS: A 72-year old patient presented with a 5-weeks-old visual acuity deterioration to excentric finger counting at half a meter. Fundoscopy showed a fibrotic macular scar, a large subretinal hemorrhage, partly recent, combined with intraretinal fluid, blood, and hard exudates. RPE-choroid graft surgery was performed, and visual acuity improved to 20/32, and maintained up until 13.5 years postoperative. Microperimetry performed at the same time revealed a 3.4 dB sensitivity, with fixation on the graft. During the postoperative years glaucoma developed, an uveitis anterior was treated, and to treat a small Coats' like lesion; one bevacizumab injection was administered. CONCLUSIONS AND IMPORTANCE: A best corrected visual acuity of 20/32 could be achieved and maintained up to 13.5 years after an RPE-choroid graft transplantation, despite an unfavorable preoperative presentation and some early and late complications. This case is a proof of principle that an RPE-choroid graft harvested from the midperiphery can support the macular metabolism up to 13.5 after surgery in a patient with severe exudative AMD. It also represents a rationale for pursuing stem cell derived RPE replacement. Anti-vascular endothelial growth factor injections are nowadays the mainstay of therapy for choroidal neovascularization and/or small hemorrhages and offer good results. Nevertheless, selected patients that cannot benefit from this therapy may profit from an autologous RPE-choroid graft transplantation.