Long-Term Outcomes of Total Exudative Retinal Detachments in Stage 3B Coats Disease.

PURPOSE: To evaluate the long-term outcomes of treatment of total exudative retinal detachments (ERDs) secondary to Coats disease (stage 3B) and the role of vitrectomy. DESIGN: Retrospective, observational case series. PARTICIPANTS: A total of 16 eyes in 16 patients undergoing treatment for total ERDs secondary to Coats disease with at least 5 years of follow-up. METHODS: We reviewed the records of patients with stage 3B Coats disease. The interventions, including the timing of vitrectomy if used, and clinical course were recorded. MAIN OUTCOME MEASURES: The primary outcome measures were visual acuity at the most recent appointment, whether there was progression to neovascular glaucoma (NVG) or phthisis bulbi, and need for enucleation. RESULTS: All patients received ablative treatment (photocoagulation or cryotherapy), with 8 having scleral buckling (SB) and 6 having external drainage of subretinal fluid (XD). Of the 12 patients who had pars plana vitrectomy (PPV), 8 had early PPV (EV) in the first year after presenting, and 4 of 8 in the expectant management group had late PPV (late vitrectomy) at a mean of 4.3 years post-presentation for treatment of significant traction retinal detachment (TRD). The other 4 patients of 8 in the expectant management group did not require vitrectomy. Mean follow-up overall was 9 1/2 years. At the date of last follow-up, 50% had no light perception or light perception vision, which was consistent across the subgroups that underwent EV (4/8), late vitrectomy (2/4), or no PPV (2/4). A total of 4 of 16 patients had progression to NVG or phthisis, 1 of whom required enucleation. CONCLUSIONS: In this retrospective series of patients with Stage 3B Coats disease, ablative therapy with a combination of PPV, XD, or SB was effective in preventing progression to NVG or phthisis in the majority of patients, thus preserving the globe. Half of the patients (4/8) in this series who did not undergo PPV in the early vitrectomy group developed late-onset TRD, suggesting a possible role for early prophylactic vitrectomy with possible SB and XD; however, this is balanced by the other half (4/8) in the expectant management group who did not require any vitrectomy.

Adjuvant Ab Interno Tumor Treatment After Proton Beam Irradiation.

PURPOSE: This study was performed to show long-term outcomes concerning globe preservation in uveal melanoma patients after proton beam therapy with the main focus on outcomes according to different adjuvant ab interno surgical procedures. DESIGN: Retrospective cohort study. METHODS: All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma between June 1998 and June 2015 were included. RESULTS: A total of 2499 patients underwent primary proton beam therapy, with local tumor control and globe preservation rates of 95.9% and 94.8% after 5 years, respectively. A total of 110 (4.4%) patients required secondary enucleation. Unresponsive neovascular glaucoma was the leading cause of secondary enucleation in 78 of the 2499 patients (3.1%). The 5-year enucleation-free survival rate was 94.8% in the endoresection group, 94.3% in the endodrainage group, and 93.5% in the comparator group. The log-rank test showed P = .014 (comparator group vs endoresection group) and P = .06 (comparator group vs endodrainage-vitrectomy group). Patients treated with endoresection or endodrainage-vitrectomy developed less radiation retinopathy (30.5% and 37.4% after 5 years, P = .001 and P = .048 [Kaplan-Meier], respectively) and less neovascular glaucoma (11.6% and 21.3% after 5 years, P = .001 and P = .01 [Kaplan-Meier], respectively) compared with the comparator group (52.3% radiation retinopathy and 57.8% neovascular glaucoma after 5 years). CONCLUSION: This study suggests that in larger tumors the enucleation and neovascular glaucoma rates might be reduced by adjuvant surgical procedures. Although endoresection is the most promising adjuvant treatment option, the endodrainage-vitrectomy is recommended in patients who are ineligible for endoresection.

A prospective, randomised, placebo-controlled, double-masked, three-armed, multicentre phase II/III trial for the Study of a Topical Treatment of Ischaemic Central Retinal Vein Occlusion to Prevent Neovascular Glaucoma - the STRONG study: study protocol for a randomised controlled trial.

BACKGROUND: Neovascular glaucoma (NVG) is rare, comprising only 3.9% of all glaucoma cases. The most common cause of NVG is ischaemic central retinal vein occlusion (iCRVO). NVG frequently results in blindness and painful end-stage glaucomatous damage leading to the need for enucleation. Currently, there is no preventive therapy for NVG following iCRVO. Rescue treatments have severe drawbacks. Accordingly, there is a great need for preventing the often visually devastating outcomes of NVG. The STRONG study is designed to test whether the topically active anti-angiogenic agent aganirsen is able to inhibit the formation of neovascularisation leading to the development of secondary NVG in eyes with iCRVO. At the same time, STRONG will provide important information on the natural course of iCRVO and NVG in a large and well-characterised cohort of such patients. METHODS/DESIGN: This protocol describes a phase II/III, prospective, randomised, placebo-controlled, double-masked, three-armed multicentre study for the investigation of aganirsen, a new topical treatment for iCRVO in order to prevent NVG. The study will evaluate the efficacy of two different doses of this newly developed antisense oligonucleotide formulated in an eye emulsion to avoid new vessel formation by blocking insulin receptor substrate-1 (IRS)-1. This leads to subsequent down-regulation of both angiogenic as well as proinflammatory growth factors such as vascular endothelial growth factor (VEGF) and tumour necrosis factor (TNF). Eligible patients (n = 333) will be treated with topical aganirsen or placebo for a period of 24 weeks. They will also be invited to participate in substudies involving analysis of gonioscopic images, detection of biomarkers for NVG and risk factors for iCRVO. DISCUSSION: The STRONG study has the potential to offer a new treatment modality for patients suffering from iCRVO with a high risk of developing NVG. The topical administration can reduce patients' burden and risk related to rescue treatment, such as destructive laser treatment or enucleation, but requires a high level of patient compliance. TRIAL REGISTRATION: EudraCT: 2014-000239-18; ClinicalTrials.gov, ID: NCT02947867 . (Registered on 15 October 2016); see also http://strong-nvg.com .

Feasibility of Proton Beam Therapy for Ocular Melanoma Using a Novel 3D Treatment Planning Technique.

PURPOSE: We evaluated sparing of normal structures using 3-dimensional (3D) treatment planning for proton therapy of ocular melanomas. METHODS AND MATERIALS: We evaluated 26 consecutive patients with choroidal melanomas on a prospective registry. Ophthalmologic work-up included fundoscopic photographs, fluorescein angiography, ultrasonographic evaluation of tumor dimensions, and magnetic resonance imaging of orbits. Three tantalum clips were placed as fiducial markers to confirm eye position for treatment. Macula, fovea, optic disc, optic nerve, ciliary body, lacrimal gland, lens, and gross tumor volume were contoured on treatment planning compute tomography scans. 3D treatment planning was performed using noncoplanar field arrangements. Patients were typically treated with 3 fields, with at least 95% of planning target volume receiving 50 GyRBE in 5 fractions. RESULTS: Tumor stage was T1a in 10 patients, T2a in 10 patients, T2b in 1 patient, T3a in 2 patients, T3b in 1 patient, and T4a in 2 patients. Acute toxicity was mild. All patients completed treatment as planned. Mean optic nerve dose was 10.1 Gy relative biological effectiveness (RBE). Ciliary body doses were higher for nasal (mean: 11.4 GyRBE) than temporal tumors (5.8 GyRBE). Median follow-up was 31 months (range: 18-40 months). Six patients developed changes which required intraocular bevacizumab or corticosteroid therapy, but only 1 patient developed neovascular glaucoma. Five patients have since died: 1 from metastatic disease and 4 from other causes. Two patients have since required enucleation: 1 due to tumor and 1 due to neovascular glaucoma. CONCLUSIONS: 3D treatment planning can be used to obtain appropriate coverage of choroidal melanomas. This technique is feasible with relatively low doses to anterior structures, and appears to have acceptable rates of local control with low risk of enucleation. Further evaluation and follow-up is needed to determine optimal dose-volume relationships for organs at risk to decrease complications rates.

Deep sclerectomy with bevacizumab and mitomycin C: a comparative study.

PURPOSE: To assess the comparative efficacy and safety of primary deep sclerectomy (DS) augmented with subconjunctival Bevacizumab and intraoperative Mitomycin C (MMC). METHODS: Retrospective, comparative case-control series of consecutive primary DS between January 2008 and December 2010. Seventy-five eyes of 73 patients were included, with 32 eyes in the MMC and 43 in the Bevacizumab group. MMC (0.2 mg/mL for 2 min) was applied subconjunctivally before scleral flap dissection. Bevacizumab (2.5 mg in 0.1 mL) was injected subconjunctivally at the end of surgery. Complete success was intraocular pressure (IOP) <19 mm Hg and a 20% decrease from baseline with no postoperative medications. RESULTS: There were no significant baseline differences between the groups. Follow-up after DS was 33.3 ± 6.1 months for the Bevacizumab and 35.0 ± 10.2 months for the MMC group (P=0.34). Complete success rates were 90.7% [95% confidence interval (CI), 82.4%-99.8%] and 87.5% (95% CI, 76.8%-99.7%) at 1 year and 76.5% (95% CI, 64.8%-90.4%) and 74.4% (95% CI, 60.5%-91.4%) at 2 years after DS in the Bevacizumab and MMC groups, respectively (P=0.52). There was no statistical difference in mean IOPs between the groups at all specified time intervals up to 2 years (P=0.28). At last follow-up 2 (6.2%) of the MMC and 2 (4.7%) eyes of Bevacizumab group were on medications to control IOP. Eighteen eyes had complications, 9 (20.9%) in Bevacizumab and 9 (28.1%) in the MMC group (P=0.8). CONCLUSION: Subconjunctival Bevacizumab with primary DS appears to be as efficacious as MMC augmentation with no additional side effects.

Prophylactic use of bevacizumab to avoid anterior segment neovascularization following proton therapy for uveal melanoma.

PURPOSE: To investigate whether the prophylactic use of bevacizumab reduces the rate of rubeosis after proton therapy for uveal melanoma and improves the possibility to treat ischemic, reapplicated retina with laser photocoagulation. DESIGN: Comparative retrospective case series. METHODS: Uveal melanoma patients with ischemic retinal detachment and treated with proton therapy were included in this institutional study. Twenty-four eyes received prophylactic intravitreal bevacizumab injections and were compared with a control group of 44 eyes without bevacizumab treatment. Bevacizumab injections were performed at the time of tantalum clip insertion and were repeated every 2 months during 6 months, and every 3 months thereafter. Ultra-widefield angiography allowed determination of the extent of retinal ischemia, which was treated with laser photocoagulation after retinal reapplication. Main outcome measures were the time to rubeosis, the time to retinal reattachment, and the time to laser photocoagulation of ischemic retina. RESULTS: Baseline characteristics were balanced between the groups, except for thicker tumors and larger retinal detachments in the bevacizumab group, potentially to the disadvantage of the study group. Nevertheless, bevacizumab prophylaxis significantly reduced the rate of iris rubeosis from 36% to 4% (log-rank test P = .02) and tended to shorten the time to retinal reapplication until laser photocoagulation of the nonperfusion areas could be performed. CONCLUSIONS: Prophylactic intravitreal bevacizumab in patients treated with proton therapy for uveal melanoma with ischemic retinal detachment prevented anterior segment neovascularization, until laser photocoagulation to the reapplied retina could be performed.

Choroidal melanoma: does endoresection prevent neovascular glaucoma in patient treated with proton beam irradiation?

PURPOSE: To evaluate the efficacy of endoresection after proton beam radiotherapy to prevent neovascular glaucoma (NVG) in patients treated for choroidal melanoma. METHODS: From a series of 4,867 patients treated for choroidal melanoma were prospectively recorded in the database (Macro Infermed 3.075). One hundred and seventy-one patients presenting a tumor diameter >10 mm and thickness >5 mm treated with proton beam (PB) radiotherapy were selected. One group of 63 patients was treated with PB therapy followed by endoresection (PE) of the scar. This group was compared with 2 historical matched controlled groups: 57 patients treated with PB therapy alone (P) and 51 patients treated with PB therapy followed by transpupillary thermotherapy of the scar (PTTT). Main outcome measures are as follows: age, gender, tumor diameter, tumor thickness, pre- and posttreatment visual acuity, NVG rate, secondary enucleation rate, and 5-year survival. Statistical analysis was performed using R version 2.5.1 software. RESULTS: Correlations between the 3 groups were P = 0.29 for age, P = 4.7×10 for tumor diameter, and P = 6.44×10 for tumor thickness. Comparison between the 3 groups showed that 2-year survival without secondary enucleation was 96.2% for PE, 88.8% for P, and 98% for PTTT (P = 0.203) (95% confidence interval). Two-year survival without NVG (95% confidence interval) was 92.7% (85.1-1.00) for PE, 54.6% for P, and 62.1% for PTTT (P = 0.0001). The difference between the endoresection (PE) group and the PB radiotherapy (P) and PB radiotherapy + TTT (PTTT) groups in terms of reduction of the NVG rate was statistically significant. Relative risk of developing NVG was calculated with the P group as reference, relative risk = 1. The relative risk of the PTTT group was 0.79 (20% reduction of the risk), and the relative risk of the PE group was 0.18 (82% reduction of the risk of developing NVG). CONCLUSION: This study shows that endoresection of the necrotic scar after PB radiotherapy reduces the risk of NVG and secondary enucleation for selected choroidal melanoma patients.

Long-term results of carbon ion radiation therapy for locally advanced or unfavorably located choroidal melanoma: usefulness of CT-based 2-port orthogonal therapy for reducing the incidence of neovascular glaucoma.

PURPOSE: To determine the long-term results of carbon ion radiation therapy (C-ion RT) in patients with choroidal melanoma, and to assess the usefulness of CT-based 2-port irradiation in reducing the risk of neovascular glaucoma (NVG). METHODS AND MATERIALS: Between January 2001 and February 2012, a total of 116 patients with locally advanced or unfavorably located choroidal melanoma received CT-based C-ion RT. Of these patients, 114 were followed up for more than 6 months and their data analyzed. The numbers of T3 and T2 patients (International Union Against Cancer [UICC], 5th edition) were 106 and 8, respectively. The total dose of C-ion RT varied from 60 to 85 GyE, with each dose given in 5 fractions. Since October 2005, 2-port therapy (51 patients) has been used in an attempt to reduce the risk of NVG. A dose-volume histogram analysis was also performed in 106 patients. RESULTS: The median follow-up was 4.6 years (range, 0.5-10.6 years). The 5-year overall survival, cause-specific survival, local control, distant metastasis-free survival, and eye retention rates were 80.4% (95% confidence interval 89.0%-71.8%), 82.2% (90.6%-73.8%), 92.8% (98.5%-87.1%), 72.1% (81.9%-62.3%), and 92.8% (98.1%-87.5%), respectively. The overall 5-year NVG incidence rate was 35.9% (25.9%-45.9%) and that of 1-port group and 2-port group were 41.6% (29.3%-54.0%) and 13.9% (3.2%-24.6%) with statistically significant difference (P<.001). The dose-volume histogram analysis showed that the average irradiated volume of the iris-ciliary body was significantly lower in the non-NVG group than in the NVG group at all dose levels, and significantly lower in the 2-port group than in the 1-port group at high dose levels. CONCLUSIONS: The long-term results of C-ion RT for choroidal melanoma are satisfactory. CT-based 2-port C-ion RT can be used to reduce the high-dose irradiated volume of the iris-ciliary body and the resulting risk of NVG.

[Treatment of neovascular glaucoma]. / Tratamentul glaucomului neovascular.

Neovascular glaucoma management is divided into preventive and curative procedures.Pre vention therapy consists of the treatment of the common underlying causes of the disease (ie diabetic retinopathy, ischemic central retinal vein occlusion and ocular ischemic syndrome) as well as the less frequent causes attributed to ocular radiation, ocular tumors, uveitis and other miscellaneous condi tions.Curative therapy includes both the neovascularization treatment and the treatment of the in creased intraocular pressure.lntravitreal Bevacizumab injection enables us to block up the neovascular trigger preparing thereby the pacient to a complement of panretinal photocoagulation or surgical treatment. Since Bevacizumab injection activity is transient, the retinal ischemia treatment by panretinal photocoagulation is mandeited in order to avoid neovascular recurrence.Short term efficacy of Bevacizumab injection is obvious with a constant, marked and swift intraocular pressure lowering espe cially in less severe and/or early forms of the disorder. In more advanced stages of neovascular glaucoma after closing the chamber angle by peripheric anterior synechiae the outcomes of this treatment are inconstant, most of cases necessitating the resorting to surgery (trabeculectomy with antifi brosis drugs or glaucoma drainage implants).

A pilot study of pars plana vitrectomy, intraocular gas, and radial neurotomy in ischaemic central retinal vein occlusion.

BACKGROUND/AIMS: There is no effective treatment for ischaemic central retinal vein occlusion (CRVO). The two major negative outcomes are neovascular glaucoma (NVG) and severe central visual loss. In this study pars plana vitrectomy (PPV), mild panretinal photocoagulation, and intraocular gas injection were employed to prevent NVG. The potential role of incision of the lamina cribrosa (radial neurotomy) for visual recovery was examined. METHODS: Eight eyes of seven patients with ischaemic CRVO had PPV, mild panretinal photocoagulation, and intraocular perfluoropropane gas injection. Four eyes had radial neurotomies performed. The patients were examined by fundus photography, fundus fluorescein angiography, optical coherence tomography, and Goldmann visual field analysis. RESULTS: No patients suffered from neovascular glaucoma. Visual recovery was seen in patients with and without neurotomy but some patients had cataract extraction to allow visualisation for PPV. Fundus photography demonstrated reduced engorgement of retinal veins in two of the patients with neurotomy and one with PPV alone. Optical coherence tomography demonstrated macular oedema in three patients with neurotomy and all patients with PPV alone. Segmental visual field loss was seen in one patient with neurotomy suggesting damage to the optic nerve head. CONCLUSIONS: PPV is safe in ischaemic CRVO. Combined with mild PRP and intraocular gas injection the risk of neovascular glaucoma is low. Neurotomy can be added to try to improve the chances of recovery of central vision but may cause additional peripheral visual field loss.

Treatment of rubeosis iridis with photodynamic therapy with verteporfin--A new therapeutic and prophylactic option for patients with the risk of neovascular glaucoma?

Patients with ischaemic retinopathy who show iris neovascularization despite panretinal laser photocoagulation (PRP) very often develop a neovascular glaucoma. Photodynamic therapy (PDT) has been shown to occlude neovascularization without damage to physiologic vessels or adjacent tissue in the treatment of choroidal neovascularization (CNV) and might also be of value for patients with neovascular glaucoma who did not benefit from the PRP. First results of a monocentre, open label, intra-individual controlled, pilot phase I/II, dose-finding study demonstrate that PDT with verteporfin is capable of occluding neovascular vessels for a defined period of time without damaging adjacent tissue or physiologic iris vessels. Whether this vessel occlusion will have an impact on the progression of rubeosis or neovascular glaucoma will be the subject of further investigation.

Diabetic iris neovascularization.

PURPOSE: To compare the validity of careful slit-lamp biomicroscopic examination of the pupillary margin to screening gonioscopic examination in the early detection and prevention of neovascular glaucoma in diabetic patients. METHODS: We examined two patients with histories of diabetes mellitus. RESULTS: Angle neovascularization developed before iris neovascularization in both patients. CONCLUSION: We believe screening gonioscopic examination is valuable in patients with diabetes.

Central vein occlusion study of photocoagulation. Manual of operations. Central Vein Occlusion Study Group.

This paper is the complete protocol (Manual of Operations) used in the Central Vein Occlusion Study (CVOS). The CVOS is a randomized clinical trial and natural history study of central retinal vein occlusion supported by the National Eye Institute. The administrative structure includes a Data and Safety Monitoring Board, 9 clinical centers, a coordinating center, and a photograph reading center. The Manual of Operations describes study design, organization, policies, and procedures. Procedures described in detail include measurement of visual acuity, fundus and iris photography, fluorescein angiography, and quality control.

Central vein occlusion study of photocoagulation therapy. Baseline findings. Central Vein Occlusion Study Group.

OBJECTIVE: Description of the patients recruited into the Central Vein Occlusion Study (CVOS) and of the status of their eyes at time of study entry. This population is currently being followed for evaluation of photocoagulation treatment for eyes with central retinal vein occlusion (CVO) and natural history. DESIGN: Prospective multicenter cohort study incorporating 2 natural history groups and 2 randomized controlled clinical trials. SETTING: Eight ophthalmic practices in the USA and 1 in France, primarily associated with academic centers. PATIENTS: Seven hundred and twenty-five patients with CVO (728 eyes) divided into 4 study groups on the basis of the perfusion status of the retina and presence of decreased vision associated with macular edema: perfused, nonperfused, indeterminate, and macular edema. INTERVENTIONS: Nonperfused group: random assignment to panretinal photocoagulation or watchful waiting. Macular edema group: random assignment to grid pattern photocoagulation or watchful waiting. Natural history groups: no intervention. MAIN OUTCOME MEASURES: Description of population and eyes based upon clinical examination and central assessment of fundus angiography, iris photographs, and stereo color fundus photographs. MAIN RESULTS: Mean age for the 725 patients is 65 years, with 43% of patients in the study age 70 or older. Despite the older age of this population, more than half (53%) of the patients are male. One hundred and eighty-one patients were randomized into the nonperfused group and 155 into the macular edema group. Follow-up in the CVOS will be completed in February 1994 when most patients are expected to have completed the planned 3 years. CONCLUSIONS: Recruitment has been successfully completed in this prospective study and the design and baseline results are presented.