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.

Novel Surgical Treatment of an Intraretinal Juxtapapillary Hemangioblastoma Using Intraocular Diathermy Forceps: A Case Report.

The surgical treatment of intraretinal juxtapapillary retinal hemangioblastomas (JRHs) was previously contraindicated because of the significant risk of collateral damage to the macula and optic nerve. This case report discusses the effectiveness and safety of a novel surgical technique using intraocular bipolar diathermy forceps to coagulate feeder and draining blood vessels of an intraretinal JRH. The patient suffered from bilateral retinal hemangioblastomas with loss of visual function in one eye and the development of an intraretinal JRH in the other eye. Despite intensive treatment with intravitreal bevacizumab and subconjunctival triamcinolone acetonide, growth of the intraretinal JRH continued, macular exudation worsened, and visual acuity decreased. Surgical treatment was undertaken in which, first, the feeder and draining vessels of the JRH were identified by comparing the retinal imaging of the JRH with the imaging before the emergence of the JRH 4 years earlier. Then, retinal incisions were made above the blood vessels and parallel to the nerve fibers during a pars plana vitrectomy. Lastly, these vessels were lifted above the retinal surface and coagulated using intraocular diathermy forceps. Postoperatively, macular edema reduced, and visual acuity increased and remained stable for about 6 months. Using intraocular diathermy forceps, this case report demonstrates effective and safe intraretinal JRH blood vessel coagulation above the retinal surface. This novel surgical approach was able to delay the deterioration of visual acuity due to tumor growth and exudation in this patient. This suggests that coagulation with intraocular diathermy forceps can be considered an additional surgical treatment option for JRHs, especially those with an intraretinal growth pattern.

Hyalocytes in proliferative vitreo-retinal diseases.

Introduction: Hyalocytes are sentinel macrophages residing within the posterior vitreous cortex anterior to the retinal inner limiting membrane (ILM). Following anomalous PVD and vitreoschisis, hyalocytes contribute to paucicellular (vitreo-macular traction syndrome, macular holes) and hypercellular (macular pucker, proliferative vitreo-retinopathy, proliferative diabetic vitreo-retinopathy) diseases. Areas covered: Studies of human tissues employing dark-field, phase, and electron microscopy; immunohistochemistry; and in vivo imaging of human hyalocytes. Expert opinion: Hyalocytes are important in early pathophysiology, stimulating cell migration and proliferation, as well as subsequent membrane contraction and vitreo-retinal traction. Targeting hyalocytes early could mitigate advanced disease. Ultimately, eliminating the role of vitreous and hyalocytes may prevent proliferative vitreo-retinal diseases entirely.

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.

Efficacy and safety of current treatment options for peripheral retinal haemangioblastomas: a systematic review.

IMPORTANCE: Approximately twenty per cent of Von Hippel-Lindau patients with retinal haemangioblastomas (RH) suffer from visual impairment. Various treatment options are available for peripheral RH. However, management of peripheral RH is complex due to multifocality and bilaterality. OBJECTIVE: To summarize published evidence on efficacy and safety of different interventions for peripheral RH and to provide treatment recommendations for specialists. EVIDENCE REVIEW: Comprehensive searches were performed using Medline, Embase, Web of Science and Google Scholar database on 4 March 2020. English publications that described outcomes related to efficacy or complications in at least two patients with peripheral RH were included. Efficacy and safety were estimated by complete tumour eradication rate, pretherapeutic and treatment-related complication rate. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to calculate the risk estimate of complications between treatment options. FINDINGS: Twenty-seven articles were included in this review describing nine different treatment options for peripheral RH: laser photocoagulation (n = 230), cryotherapy (n = 50), plaque radiotherapy (n = 27), vitreoretinal surgery (n = 88), photodynamic therapy (PDT; n = 14), transpupillary thermotherapy (TTT; n = 10), external beam radiotherapy (n = 3), systemic treatment (n = 7) and intravitreal anti-VEGF (n = 2). Complete tumour eradication was achieved in 86.7% (95% CI: 83.5-89.9%) of all eyes. For the different treatments, this was after laser photocoagulation 89.9% (86.1-93.7%), cryotherapy 70.2% (57.0-83.4%), plaque radiotherapy 96.3% (89.1-100.0%), vitreoretinal surgery (100.0%), PDT 64.3% (38.3-90.3%) and TTT 80.0% (53.8-100.0%). No complete tumour eradication was achieved after systemic therapy, external beam radiotherapy or intravitreal anti-VEGF. Photodynamic therapy and vitreoretinal surgery showed the highest complication rate after treatment compared to the other treatments (OR 10.5 [95% CI: 2.9-38.4]) and (OR 5.9 [95% CI: 3.4-9.9]), respectively. Cases that had pretherapeutic complications showed a higher treatment-related complication rate (OR 14.8 [95% CI: 7.3-30.0]) than cases without complications before treatment. CONCLUSIONS AND RELEVANCE: These findings suggest that laser photocoagulation is the safest and most effective treatment method for peripheral RH up to 1.5 mm in diameter. Vitreoretinal surgery has the highest success rate for complete tumour eradication and may be the most suitable treatment option in the presence of pretherapeutic complications and for larger tumours.

[Acute onset of floaters, even without flashes, is an urgent ophthalmic warning sign]. / Plotse toename van mouches volantes is een alarmsymptoom, ook zónder lichtflitsen.

Acute onset of floaters is most likely caused by a posterior vitreous detachment (PVD). A PVD can lead to a retinal tear and subsequently to a retinal detachment with permanent vision loss if left untreated. A patient who presents to a primary care physician with acute onset of floaters, in the absence flashes or visual field loss, is often referred to an ophthalmologist without urgency. In the current Dutch general practitioners standard, acute onset or increase of floaters, without flashes or visual loss, is not included as a reason for urgent referral to an ophthalmologist. Patients who present with acute onset of floaters without flashes have a 14-23% risk of having a retinal tear. Risk factors for developing a retinal tear are high myopia, trauma, cataract surgery, or a retinal tear or retinal detachment in the past medical or family history. Patients with acute onset of floaters should be triaged for urgent ophthalmologic assessment.

Surgery for Combined Hamartoma of the Retina and Retinal Pigment Epithelium.

There is no consensus on whether and when surgical treatment is indicated for combined hamartoma of the retina and retinal pigment epithelium (CHRRPE). We aim to discuss the benefits of surgical intervention and techniques that may improve the outcome. A 24-year-old man experienced progressive visual loss for 6 months in his left eye due to CHRRPE. At presentation, visual acuity was 1.3 LogMAR and fundoscopy revealed extensive tractional pre- and epiretinal membranes, subretinal exudation, and a vasoproliferative tumor in the inferior periphery. A complete vitrectomy was performed, while paying special attention to vitreous shaving at the vitreous base and removal of vitreoschisis-induced vitreous cortex remnants (VCR) from the retinal surface posterior to the vitreous base. Tractional membranes and internal limiting membrane were peeled, and the vasoproliferative tumor was excised. Silicone oil tamponade was removed 11 weeks after surgery. No intra- or postoperative complications occurred. Visual acuity improved to 0.8 LogMAR and remained stable for 48-month follow-up. Vitreoretinal surgery can prevent complications that occur with CHRRPE. In addition, visual function may improve even if the initial visual acuity is low. Timely and complete vitrectomy with extensive membranectomy and detection and removal of VCR is recommended to avoid complications in challenging CHRRPE.

The role of vitreous cortex remnants in proliferative vitreoretinopathy formation demonstrated by histopathology: A case report.

PURPOSE: The pathogenesis of proliferative vitreoretinopathy (PVR), the most important cause of retinal detachment surgery failure, is still not fully understood. We previously hypothesized a causal link between vitreoschisis-induced vitreous cortex remnants (VCR) and PVR formation. The purpose of this case report is to demonstrate this association by showing the clinical occurrence of PVR in the presence of VCR across the retinal surface, illustrated by histopathological analysis. OBSERVATIONS: A 69-year-old male was referred because of widespread epiretinal membrane formation after treatment of recurrent retinal detachments. During surgery with extensive membrane peeling, a large continuous membrane was peeled from the superior arcade towards the inferior temporal mid-periphery. Histopathological analysis of this membrane revealed areas with different characteristics: paucicellular laminar collagen-rich areas, suggestive for VCR, areas with increased cellularity, and more fibrotic areas with low cellularity.The immunohistochemical analysis identified cell type variety in these areas: collagen-rich areas showed glial cells and hyalocytes, while in areas with high cellularity fibroblasts, macrophages and retinal pigment epithelial cells were found, which have previously been shown to play an important role in the development of PVR as they can transdifferentiate into myofibroblasts, which were seen in the more fibrotic areas. CONCLUSIONS AND IMPORTANCE: These findings support the theory that VCR have a role in PVR development, where VCR can act as a scaffold for fibrocellular proliferation. We suggest 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 retinal detachment surgery.

Retinal haemangioblastomas in von Hippel-Lindau germline mutation carriers: progression, complications and treatment outcome.

PURPOSE: Evaluation of phenotype and treatment outcome of retinal haemangioblastomas (RH) in von Hippel-Lindau (VHL) disease and correlation of these features with the genotype of VHL germline mutation carriers. METHODS: Retrospective analysis of a longitudinal cohort of 21 VHL germline mutation carriers and RH. Clinical and genetic data were obtained to analyse the correlation of genotype with phenotype and treatment outcomes. RESULTS: All patients were categorized in two genotypic categories: missense mutations (MM) and truncating mutations (TM). Mean follow-up duration was 16.3 years and did not differ significantly between mutation groups (p = 0.383). Missense mutations (MM) carriers (n = 6) developed more progression-related complications compared to TM carriers (n = 15) (p = 0.046). Vitreoretinal surgery was more often applied in MM carriers (p = 0.036). Moderate (visual acuity (VA)20/80 to 20/200) to severe (VA < 20/200) visual impairment was observed in 53.3% of the eyes of MM carriers and 28.1% of the eyes of TM carriers at last recorded visit. CONCLUSION: Missense mutations in VHL patients seem to have a higher prevalence of progression-related complications. Missense mutations (MM) carriers required therefore more often vitreoretinal surgical treatment with a worse treatment outcome. Genetic analysis may play a role in determining a pro-active treatment strategy and prognosis for RH.

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.

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.

Classification and treatment follow-up of a juxtapapillary retinal hemangioblastoma with optical coherence tomography angiography.

PURPOSE: Only an endophytic growth pattern in juxtapapillary retinal hemangioblastoma (JRH) is an indication for surgical treatment, but classification of growth types is difficult using conventional imaging techniques. This case report describes the use of optical coherence tomography angiography (OCT-A) features for classification and treatment follow-up in a case with JRH. OBSERVATIONS: The JRH of this patient was easily detected with two different OCT-A methods in both en-face and cross-sectional B-scan images, and was classified as a sessile growth type. This growth type excluded the treatment option of vitreoretinal surgery with excision of the lesion or ligation of the feeder vessels. The patient was treated multiple times with intravitreal bevacizumab. Treatment follow-up with OCT-A initially revealed a stable extent of the JRH, with some slight flow deviations in en-face visualization, followed by a period of progressive growth of the lesion. CONCLUSIONS: OCT-A revealed the depth localization of the JRH and seems to be a valuable tool for JRH classification. Detailed classification may be useful when surgery is considered as a treatment strategy. Furthermore, treatment follow-up is possible with OCT-A, although imaging artifacts should be taken into account.

Symptoms related to posterior vitreous detachment and the risk of developing retinal tears: a systematic review.

Flashes and floaters are the hallmark symptoms of a posterior vitreous detachment (PVD) which itself is related to an increased risk of the development of retinal tears, retinal detachment and vitreous haemorrhage. The aim of this study is to assess the associations between different symptoms related to PVD and the risk of developing retinal tears. A systematic review of articles written in English, using MEDLINE, Embase (via Embase.com) and the Cochrane Controlled Trials Register (1996-2017) was conducted. Search terms included five elements: PVD, retinal tears, retinal detachment, floaters and flashes. Independent extraction of articles was conducted by two authors using predefined data fields, including study quality indicators. Thirteen studies fulfilled the selection criteria. Analysis of pooled data revealed that presence of isolated flashes was associated with the development of retinal tears in 5.3% of symptomatic eyes [mean 2.9 eyes; 95% CI (2.1, 5.7)].Conversely, floaters alone had a stronger association with retinal tears (16.5% of eyes), as compared to flashes. The association to retinal tears was even greater for those patients reporting both flashes and floaters [mean 17.8 eyes (20.0%); 95% CI (17.4, 18.1)]. Retinal and/or vitreous haemorrhage was also associated with the presence and later development of retinal tears [mean 12.5 eyes (30.0%); 95% CI (11.7, 13.9)]. Patients with more than 10 floaters or a cloud in their vision had a high risk of developing retinal tears (OR19.8, p-value 0.032). In the setting of a PVD, the onset of flashes and floaters, and the presence of retinal and/or vitreous haemorrhage are risk factors for the development of retinal tears. The association is greater when both symptoms are present, and even greater when the patient reports more than 10 floaters, a curtain or a cloud and/or there is a positive finding of a vitreous or retinal haemorrhage. This study supports the necessity of an immediate examination of patients presenting with symptoms related to a PVD, and a follow-up examination might be prudent in a subgroup of these patients.

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.

Intra-ocular diathermy forceps.

PURPOSE: The purpose of this study was to develop intra-ocular diathermy forceps and test them on perfused porcine cadaver eyes. METHODS: We designed two types of 23-gauge intra-ocular bipolar diathermy forceps by modifying commercially available membrane peeling forceps. In the first type, the emitting electrode is connected to one-half of the core and the return electrode to the other half, with one jaw of the forceps attached to each half. In the second type, the emitting electrode is attached to the core and both jaws of the forceps, and the return electrode to the surrounding tube. We compared the new diathermy forceps to conventional intra-ocular diathermy, on perfused porcine cadaver eyes. First-order retinal artery and vein closure was confirmed both by a perfusion study and by histology of the treated vessels. RESULTS: Type 1 diathermy forceps closed retinal arteries and veins more successfully (five of five and five of five successful treatments, respectively) than Type 2 diathermy forceps (five of five and four of five, respectively) and conventional diathermy (three of five and four of five, respectively). Less energy was used with Type 1 compared to Type 2 and conventional for artery closure (1.5 ± 0.0 versus 4.6 ± 3.3 versus 2.1 ± 0.8 joules, respectively) and vein closure (1.5 ± 0.0 versus 5.4 ± 4.6 versus 2.4 ± 0.8 joules, respectively). Histology of the treated vessels confirmed the perfusion study results. CONCLUSION: We designed two types of a new multifunctional intra-ocular instrument with the ability to peel membranes and to grasp, compress and coagulate retinal blood vessels. Both types pose operational advantages compared to current conventional intra-ocular diathermy.