Vitreoschisis-induced vitreous cortex remnants in proliferative vitreoretinopathy: A comprehensive review from basic research to clinical practice.

Proliferative vitreoretinopathy (PVR) significantly impacts the prognosis of rhegmatogenous retinal detachment (RRD), one of the most critical and increasing causes of vision loss in the Western world. Despite advancements in surgical instruments and techniques, the failure rate due to PVR remains substantial, necessitating additional surgeries and often leading to unsatisfactory visual outcomes. This comprehensive review explores the role of vitreoschisis-induced vitreous cortex remnants (VCR) as a critical, previously under-recognised factor contributing to PVR. Vitreoschisis, a phenomenon where the inner lamellae of the posterior vitreous cortex detach while the outermost layers remain attached to the retina, creates VCR that may contain hyalocytes and serve as scaffolds for fibrocellular proliferation. These remnants are difficult to visualise without triamcinolone acetonide (TA) staining, leading to their frequent lack of recognition in clinical practice. Moreover, removing VCR can be challenging and time-consuming, often requiring meticulous surgical techniques to avoid retinal damage and ensure complete elimination. This review consolidates insights from basic research and clinical practice, emphasising the importance of complete vitreous removal and effective VCR detection and removal to mitigate PVR risks. It highlights the histopathological and clinical evidence supporting the hypothesis that VCR, containing hyalocytes, play a pivotal role in preretinal membrane formation. The review also discusses epidemiological data, surgical management strategies and potential future directions, including improved visualisation techniques and the development of new surgical tools and methods. This review aims to improve surgical outcomes and reduce the frequency and burden of RRD-related complications by addressing VCR as a critical factor in PVR.

Natural History and Surgical Outcomes of Lamellar Macular Holes.

PURPOSE: To assess the natural history and surgical outcomes of lamellar macular holes (LMHs). DESIGN: Retrospective and consecutive case series. SUBJECTS: Patients with LMHs from multiple tertiary care centers. METHODS: Clinical charts and OCT scans were reviewed. MAIN OUTCOME MEASURES: The visual acuity (VA) changes and the occurrence rate of full-thickness macular hole (FTMH) were studied in both groups. Within the operated group, factors associated with 6-month VA and development of FTMH were explored. RESULTS: One hundred seventy-eight eyes were included, of which 89 were monitored and 89 underwent surgery. In the observation group, the mean VA decreased from 0.25 ± 0.18 to 0.28 ± 0.18 logarithm of the minimum angle of resolution (logMAR; P = 0.13), with 14 eyes (15.7%) that lost ≥ 0.2 logMAR VA, after 45.7 ± 33.3 months. Nine eyes (10.1%) spontaneously developed an FTMH. In the operated group, the mean VA increased from 0.47 ± 0.23 to 0.35 ± 0.25 logMAR at 6 months (P < 0.001) and 0.36 ± 0.28 logMAR (P = 0.001) after 24.1 ± 30.1 months. By multivariate analysis, better baseline VA (P < 0.001), the presence of an epiretinal membrane (P = 0.03), and the peeling of the internal limiting membrane (ILM; P = 0.02), with a greater effect of ILM perihole sparing, were associated with a greater 6-month VA. Perihole epiretinal proliferation sparing was associated with a better postoperative VA by univariate analysis (P = 0.03), but this was not significant by multivariate analysis. Eight eyes (9.0%) developed a postoperative FTMH. Using Cox proportional hazard ratios [HRs], pseudophakia at baseline (HR, 0.06; 95% confidence interval [CI], 0.00-0.75; P = 0.03) and peeling of the ILM (HR, 0.05; 95% CI, 0.01-0.39; P = 0.004) were protective factors, while ellipsoid zone disruption (HR, 10.5; 95% CI, 1.04-105; P = 0.05) was associated with an increased risk of FTMH. CONCLUSION: Observed eyes with LMH experienced, on average, progressive VA loss. Patients with LMH and altered vision may benefit from surgery. Internal limiting membrane peeling, with perihole ILM sparing, represents a crucial step of the surgery associated with a greater VA and a lower risk of postoperative FTMH. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Novel insights into the pathophysiology of proliferative vitreoretinopathy: The role of vitreoschisis-induced vitreous cortex remnants.

PURPOSE: We previously hypothesized a causal relationship between vitreoschisis-induced vitreous cortex remnants (VCR) and the development of proliferative vitreoretinopathy (PVR). This study aims to substantiate this association through histopathological analysis of surgical specimens in support of strategies to improve therapeutic outcomes. METHODS: A descriptive, prospective, non-consecutive case series. Histopathological and immunohistochemical analyses were performed on membranes removed from the peripheral retinal surface during initial vitrectomy for primary rhegmatogenous retinal detachment (RRD) (n = 11) or recurrent retinal detachment (n = 12). The clinical aspect of the membranes ranged from loose-meshed membranes visualized with triamcinolone to more fibrotic membranes stained with trypan blue. RESULTS: Consistent with the clinical presentation, histopathological analysis revealed membranes with different area characteristics. Paucicellular lamellar collagen-rich areas, suggestive of VCR, appeared to transition to areas of increased cellularity and eventually more fibrotic areas of low cellularity. Five different area characteristics could be identified that seemed to correspond to five histopathological stages in PVR formation, with lamellar VCR collagen acting as an essential precondition: 1. Lamellar collagen, low cellularity (hyalocytes). 2. Lamellar collagen, increased cellularity (hyalocytes, glial cells). 3. Lamellar collagen, high cellularity (macrophages, glial cells, RPE-cells). 4. Early fibrosis, decreased cellularity (myofibroblasts). 5. Fibrosis, low cellularity (myofibroblasts). CONCLUSION: These findings confirm the role of VCR in preretinal PVR formation posterior to the vitreous base. We propose that the presence of VCR over the retinal surface should be qualified as a risk factor for PVR formation. Detection and adequate removal of VCR may improve the success rate of vitreoretinal surgeries.

Globe Fixation Caused by Intraocular Migration of an Orbital Floor Implant.

A 30-year-old male presented with diplopia 1 month after implantation of an orbital floor plate for a blowout fracture. The orbital plate was removed 3 months later, however, the fixation bar was left in place as it had migrated full thickness through the inferior oblique muscle, sclera, choroid, and retina. After 5 years of head tilt, the patient was referred to our department with a metallic intraocular foreign body visible in fundo and an important elevation deficit. CT imaging confirmed our clinical suspicion of a retained fixation bar. The extraocular part of the fixation bar was removed via a transconjunctival inferior orbitotomy, leaving the intraocular part in place due to the high risk of ocular complications upon removal. Postoperative ocular motility improved greatly and the patient no longer experiences diplopia in daily life. Orbital plate migration is a rare complication that should be considered in de novo diplopia after orbital reconstruction.

Active removal of anterior segment-migrated dexamethasone implant (Ozurdex®).

Background: Ozurdex® (Allergan plc., Dublin, Ireland) is an intravitreal sustained-release dexamethasone (DEX) implant. The implant has been reported to migrate into the anterior chamber, potentially causing corneal decompensation. Prompt removal or relocation in the vitreous cavity is advised but troublesome due to its fragility. Several techniques exist, but elaborate setup and specialized surgical skills that are required may cause delay in treatment. We report a novel technique that avoids these shortcomings. Case presentation: A 59-year-old woman presented to the emergency department with visual loss due to an anterior chamber-migrated DEX implant and corneal edema. Using an ophthalmic viscosurgical device (OVD) and a bent 19-gauge needle, the implant has promptly been removed in a one-minute procedure under topical anesthesia. Conclusion: Aspirating an anterior chamber-migrated DEX implant using a 19-gauge bent needle is a cost-effective, time-efficient and safe technique, not requiring specialized surgical skills.

AUTOLOGOUS NEUROSENSORY RETINAL TRANSPLANT TO TREAT REFRACTORY SEROUS RETINAL DETACHMENT SECONDARY TO OPTIC DISK COLOBOMA.

PURPOSE: To describe a novel surgical technique to treat refractory serous retinal detachment in a patient with an optic disk coloboma. METHODS: Case report. RESULTS: A 32-year-old male patient with an optic disk coloboma in his right eye was referred for recurrent retinoschisis and serous macular detachment despite multiple vitrectomies. Previous surgical procedures included peeling of internal limiting membrane and juxtapapillary laser as well as different tamponade agents such as sulfur hexafluoride gas, standard silicone oil, and heavy silicone oil. Our first approach to close the cavity using autologous platelet concentrate and gas tamponade was also unsuccessful with early recurrence of the submacular fluid. In a second attempt, an autologous neurosensory retinal transplant was used to cover the optic disk cavity. At 17-month follow-up, the macula was still attached. As a postoperative complication, the patient developed high intraocular pressure, for which laser cycloablation eventually was necessary. CONCLUSION: Autologous neurosensory retinal transplant may be a reasonable treatment option for patients with recurrent optic disk cavity-associated maculopathy.

Occurrence of Macular Neovascularization after Retinal Pigment Epithelium-Choroid Translocation Surgery to Treat Complicated Age-Related Macular Degeneration: Incidence, Management, and Outcome.

INTRODUCTION: This study investigates the incidence, clinical characteristics, and treatment response of macular neovascularization (MNV) occurring after retinal pigment epithelium (RPE) and choroid graft translocation surgery (RPE-choroid TS). METHODS: Retrospective analysis of 36 eyes of 36 consecutive patients who underwent RPE-choroid TS. Longer term follow-up of graft survival focusing on the occurrence of MNV was performed using multimodal imaging. RESULTS: Indications for RPE-choroid TS included complications of neovascular age-related macular degeneration in 34 patients and drusenoid pigment epithelial detachment in 2 patients. With a mean follow-up of 30 months, 8 patients out of 36 developed signs of MNV. Of these 8 patients, 4 presented with a drop in visual acuity (VA) due to centrally located type 3 MNV. Early diagnosis and treatment prevented significant functional consequences. Four patients developed type 2 MNV at the border of the graft, which did not tend to affect the VA. CONCLUSION: We report a high incidence of MNV after RPE-choroid TS. Early diagnosis and treatment may preserve function in these patients. The type of MNV and location can be used to guide the management.

Autologous full-thickness RPE-choroid graft to treat high-risk drusenoid pigment epithelial detachment without CNV.

Objective: To report on the survival of a retinal pigment epithelium (RPE)-choroid graft translocated to treat a patient with drusenoid pigment epithelial detachment (DPED). Methods: We describe a patient with bilateral high-risk DPED where one eye was treated with RPE-choroid translocation surgery and followed up for more than two years. Results: The RPE-choroid graft surgery was straightforward and the fully perfused graft was able to support stable vision of 0.5 Snellen acuity for more than two years despite the development of a choroidal neovessel at the edge of the graft. The vision in the fellow eye dropped from 0.5 to 0.2 Snellen in the same period. Conclusion: RPE-choroid translocation may slow the progression of DPED to atrophy but it can also transform dry age-related macular degeneration (AMD) into neovascular AMD.

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.

A prospective multicentre randomized placebo-controlled superiority trial in patients with suspected bacterial endophthalmitis after cataract surgery on the adjuvant use of intravitreal dexamethasone to intravitreal antibiotics.

PURPOSE: We aimed to determine whether intravitreal dexamethasone as an adjuvant to intravitreal antibiotics is beneficial in the treatment of suspected bacterial endophthalmitis after cataract surgery. METHODS: Randomized, placebo-controlled superiority trial in three tertiary referral centres in the Netherlands. Patients with suspected bacterial endophthalmitis within 6 weeks after cataract surgery were eligible. A diagnostic vitreous biopsy was taken for culture, and patients received intravitreal injections of 400 µg dexamethasone (without preservatives) or placebo, in addition to 0.2 mg vancomycin and 0.05 mg gentamicin. The vancomycin and dexamethasone or placebo injections were repeated once at day 3 or 4. Primary outcome measure was best-corrected visual acuity (BCVA) at 1 year. RESULTS: Between 1 November 2004 and 1 March 2014 (excluding two interruptions totalling 20 months), 324 eligible patients presented. A total of 167 patients (81 dexamethasone, 86 placebo) were available for the intention-to-treat analysis. Biopsies of 114 patients (68%) were culture-positive. Final BCVA did not differ between the dexamethasone and the placebo group (logMAR 0.31 ± 0.58 versus 0.27 ± 0.50; p = 0.90), nor did the number of patients with final vision of no light perception (LP, 7 versus 13). Pain, corneal oedema, the absence of a red fundus reflex on presentation, LP on presentation and culture of virulent pathogens from biopsy were statistically significantly associated with an unfavourable visual outcome. CONCLUSION: Intravitreal dexamethasone without preservatives as an adjuvant to intravitreal antibiotics does not improve visual acuity (VA) in patients treated for suspected bacterial endophthalmitis after cataract surgery.

Clonidine as an adjuvant to prolong local analgesia in conventional scleral buckle surgery.

PURPOSE: The aim of this study was to determine the effect of a single dose of 150 µg of clonidine as an adjuvant to levobupivacaine (Chirocaine(®)) in retrobulbar block on postoperative safety and analgesia. METHODS: This was a prospective, randomized, controlled, double-blind trial. One hundred twenty patients with a rhegmatogenous retinal detachment scheduled to undergo external buckling surgery and cryocoagulation were asked to participate. Participants were randomly assigned either to receive 3-5 mL Chirocaine (22.5-37.5 mg) or 3-5 mL Chirocaine and 1 mL clonidine (150 µg) before surgery. Main outcome measures were postoperative pain, use of analgesics, blood pressure, and plasma clonidine concentration. Nine nonrandomized patients consented to give blood samples for pharmacokinetic analysis. RESULTS: There was no significant difference in pain score between both groups. On average, the use of analgesic medication occurred later in the clonidine group (P=0.0004), but there was no statistical difference in the first time that postoperative medication was taken (P=0.13). Blood pressure was reduced by clonidine (systolic: P=0.02, diastolic: P=0.006). Clonidine levels could be demonstrated during the 24-h postoperative period, with an average half-life of 22 h. CONCLUSIONS: Administration of clonidine as an adjuvant to conventional retrobulbar block is safe, and delays the postoperative use of analgesics. The reduction of postoperative pain and the time of first use of analgesic medication, however, were not significantly different between groups. Further, pain scores in both study groups remained low. Therefore, the beneficial effect of clonidine in conventional scleral buckle surgery appears to be limited.

A prospective multicenter randomized placebo-controlled trial of dexamethasone as an adjuvant in the treatment of postoperative bacterial endophthalmitis: interim safety analysis of the study drug and analysis of overall treatment results.

PURPOSE: In an ongoing prospective multicenter randomised placebo-controlled trial we study the adjuvant use of intravitreal dexamethasone in the treatment of patients with suspected bacterial endophthalmitis after phacoemulsification. In accordance with the study protocol, a mid-inclusion interim analysis of the safety of the study drug was performed. PATIENTS AND METHODS: Patients with suspected endophthalmitis after phacoemulsification were asked to participate in this study. A diagnostic vitreous biopsy was taken and the patients received intravitreal injections of 400 micrograms dexamethasone or a placebo, plus 0.2 mg vancomycin and 0.05 mg gentamicin. Injections were repeated after 3 or 4 days. The safety analysis included: the number of eyes with an evisceration; no light perception; or a visual acuity of less than 5/200. Treatment outcome was evaluated in terms of: the percentage of patients with a visual acuity of 20/40 or more and 20/100 or more. RESULTS: The interim analysis included 81 patients with at least 1 year follow-up. Sixty-three patients (65 %) were culture-positive. Safety analysis: 7 eyes were eviscerated (3 dexamethasone, 4 placebo); 4 eyes had no light perception (2 dexamethasone, 2 placebo); and 4 eyes had less than 5/200 vision (3 dexamethasone, 1 placebo). Treatment outcome: 70 % of patients had a visual acuity of at least 20/40. CONCLUSION: The safety analysis does not warrant premature discontinuation of the study. So far, the overall outcome of our treatment regimen, consisting of merely a diagnostic biopsy instead of a vitrectomy and an optimized antibiotic dosing, compares favourably to published literature.

Deferred laser photocoagulation of relaxing retinotomies under silicone oil tamponade to reduce recurrent macular detachment in severe proliferative vitreoretinopathy.

PURPOSE: This study sought to investigate whether, in patients with retinal detachment complicated by proliferative vitreoretinopathy, we can re-attach the retina with a posterior relaxing retinotomy and silicone oil tamponade while postponing laser retinopexy for several months. METHODS: In 13 consecutive patients we applied laser coagulation of the retinotomy edge 15 ± 12 weeks after surgery. Silicone oil was removed 9 ± 6 weeks after laser application. RESULTS: After the retinotomy without laser, some degree of central shifting was seen in all patients, followed by obvious curling in 10 patients. The total follow-up was 24 ± 7 months after retinotomy and 13 ± 9 months after oil removal. The retina was attached in 12 patients at the last visit, with the oil still in situ in three patients. Seven patients, however, required additional surgery. Function remained stable with a mean preoperative and postoperative Snellen visual acuity of 0.09. CONCLUSIONS: Not anchoring retinotomy edges with a laser at the time of surgery allows inward curling and central slippage of retinal edges under silicone oil. This appears to compensate for the retinal fibrosis occurring in the weeks following surgery and may result in less macula-off re-detachments under oil, and potentially, in better visual outcome.

Novel 'heavy' dyes for retinal membrane staining during macular surgery: multicenter clinical assessment.

PURPOSE: To evaluate the feasibility of two novel 'heavy' dye solutions for staining the internal limiting membrane (ILM) and epiretinal membranes (ERMs), without the need for a prior fluid-air exchange, during macular surgery. METHODS: In this prospective nonrandomized multicenter cohort study, the high molecular weight dyes ILM-Blue™ [0.025% brilliant blue G, 4% polyethylene glycol (PEG)] and MembraneBlue-Dual™ (0.15% trypan blue, 0.025% brilliant blue G, 4% PEG) were randomly used in vitrectomy surgeries for macular disease in 127 eyes of 127 patients. Dye enhanced membrane visualization of the ILM and ERMs, 'ease of membrane peeling', visually detectable perioperative retinal damage, postoperative best-corrected visual acuity (BCVA), dye remnants and other unexpected clinical events were documented by 21 surgeons. RESULTS: All surgeries were uneventful, and a clear bluish staining, facilitating the identification, delineation and removal of the ILM and ERMs, was reported in all but five cases. None of the surgeries required a fluid-air exchange to assist the dye application. BCVA at 1 month after surgery improved in 83% of the eyes in the MembraneBlue-Dual™ group and in 88% in the ILM-Blue™ group. No dye remnants were detected by ophthalmoscopy, and no retinal adverse effects related to the surgery or use of the dyes were observed. CONCLUSION: The 'heavy' dye solutions ILM-Blue™ and MembraneBlue-Dual™ can be injected into a fluid-filled vitreous cavity and may facilitate staining and removal of the ILM and/or ERMs in macular surgery without an additional fluid-air exchange.

Autosomal recessive Stickler syndrome in two families is caused by mutations in the COL9A1 gene.

PURPOSE: To investigate COL9A1 in two families suggestive of autosomal recessive Stickler syndrome and to delineate the associated phenotype. METHODS: The probands of two consanguineous autosomal recessive Stickler families were evaluated for homozygosity using SNP microarray in one and haplotype analysis in the other. Subsequently, the entire COL9A1 open reading frame was analyzed by DNA sequencing in all members of the respective families. Several family members were investigated for dysmorphic features as well as ophthalmic, audiologic, and radiologic abnormalities. RESULTS: A novel homozygous COL9A1 mutation (p.R507X) was identified in two affected Turkish sisters, and the previously published mutation (p.R295X) was found in a Moroccan boy. Ophthalmic assessment revealed myopia, cataracts, distinct vitreous changes, progressive chorioretinal degeneration, and exudative and rhegmatogenous retinal detachments. All three had sensorineural hearing loss and epiphyseal dysplasia. Intervertebral disc bulging was observed in one patient and in two heterozygous carriers of the p.R507X mutation. CONCLUSIONS: A second, novel mutation was identified in COL9A1, causing autosomal recessive Stickler syndrome together with the previously described nucleotide change in two separate families. Although the overall phenotype was comparable to autosomal dominant Stickler, vitreous changes that may enable recognition of patients who are likely to carry mutations in COL9A1 were identified, and exudative retinal detachment was observed as a new finding in Stickler syndrome.

The effect of a preoperative subconjuntival injection of dexamethasone on blood-retinal barrier breakdown following scleral buckling retinal detachment surgery: a prospective randomized placebo-controlled double blind clinical trial.

BACKGROUND: Blood-retinal barrier breakdown secondary to retinal detachment and retinal detachment repair is a factor in the pathogenesis of proliferative vitreoretinopathy (PVR). We wished to investigate whether an estimated 700 to 1000 ng/ml subretinal dexamethasone concentration at the time of surgery would decrease the blood-retinal barrier breakdown postoperatively. METHODS: Prospective, placebo-controlled, double blind clinical trial. In 34 patients with rhegmatogenous retinal detachment scheduled for conventional scleral buckling retinal detachment surgery, a subconjunctival injection of 0.5 ml dexamethasone diphosphate (10 mg) or 0.5 ml placebo was given 5-6 hours before surgery. Differences in laser flare photometry (KOWA) measurements taken 1, 3 and 6 weeks after randomisation between dexamethasone and placebo were analysed using mixed model ANOVA, while correcting for the preoperative flare measurement. RESULTS: Six patients did not complete the study, one because of recurrent detachment within 1 week, and five because they missed their postoperative laser flare visits. The use of dexamethasone resulted in a statistically significant decrease in laser flare measurements at the 1-week postoperative visit. CONCLUSION: The use of a preoperative subconjunctival injection of dexamethasone decreased 1-week postoperative blood-retina barrier breakdown in patients undergoing conventional scleral buckling retinal detachment surgery. This steroid priming could be useful as a part of a peri-operative regime that would aim at decreasing the incidence of PVR.