Peripheral extent of the choroidal circulation by ultra-widefield indocyanine green angiography in healthy eyes.

AIM: To analyse the peripheral extent of choroidal circulation using ultra-widefield (UWF) indocyanine green angiography (ICGA) in healthy eyes. METHODS: UWF ICGA images of 55 eyes of 36 healthy subjects were captured using the Optos California (Optos, Dunfermline, United Kingdom) in this prospective observational study. Images were analysed to locate the peripheral extent of the visible choroidal circulation, and the boundary was marked in ImageJ (v1.52). Each pixel annotated as the border of the choroidal circulation was projected individually to its anatomically correct location on the three-dimensional model eye, and spherical trigonometry was applied (using the Optos software) to calculate its respective radial distance from the centre of the optic disc in metric units (corrected by stereographic projection) for each quadrant. RESULTS: The mean area of the peripheral extent was estimated to be 893.2 mm2 (95% CI: 844.2 to 942.3 mm2). The mean distance (range) of this boundary from optic nerve centre was 18.22 mm (95% CI: 14.0 to 23.14 mm). Multiple regression analysis with age, gender, axial length or ethnicity showed no relationship. There was excellent inter-grader reproducibility, with intraclass correlation coefficients of 0.95 (95% CI: 0.80 to 0.99, p<0.001) for distance and 0.99 (95% CI: 0.988 to 0.999, p<0.001) for area measurements. CONCLUSIONS: The peripheral choroidal boundary may be defined using UWF ICGA. Knowledge of the normal extent and its variability is essential to understand the impact of disease on the choroidal vasculature.

Distribution and Location of Vortex Vein Ampullae in Healthy Human Eyes as Assessed by Ultra-Widefield Indocyanine Green Angiography.

PURPOSE: To study the number and distribution of vortex ampullae in healthy eyes using ultra-wide field (UWF) indocyanine green angiography (ICGA). DESIGN: Prospective, observational study. PARTICIPANTS: Thirty-six eyes of 36 healthy participants with no evidence of ocular or systemic disease. METHODS: The UWF ICGA images (central and peripheral steered) were captured using the Optos California (Optos, Dunfermline, United Kingdom) instrument. The images were projected stereographically to correct for peripheral distortion and obtain accurate measurements. All images were graded and analyzed for number, location, and distance of the vortex vein ampullae from the center of optic nerve. MAIN OUTCOME MEASURES: Mean number and the distance of ampullae from the center of optic nerve in all quadrants. RESULTS: The mean number of ampullae observed by UWF ICGA was 8.0±2.1 (range, 5-13). The mean distance of a vortex vein ampulla from the optic nerve was 14.2±1.1 mm (range, 10.3-17.7 mm). The frequency of ampullae was higher in the superior and inferior quadrants than the nasal and temporal quadrants. Ampullae were never observed in the 3- or 9-o'clock meridians. Multiple regression analysis showed no relationship with age, gender, axial length, or ethnicity. Excellent intergrader reproducibility was found between graders with an intraclass correlation coefficient (distance measurements: intraclass correlation coefficient, 0.99; 95% CI, 0.979-0.999; P < 0.001; number of ampullae: intraclass correlation coefficient, 0.99; 95% CI, 0.988-0.999; P < 0.001). CONCLUSIONS: The number of discrete vortex vein ampullae that can be discerned by UWF ICGA in healthy individuals is greater frequently and substantially than the 4 that are traditionally thought to drain the major quadrants. Considerable variability in the number and position of the ampullae may be apparent in healthy individuals.

LONG-TERM OUTCOMES IN PATIENTS WITH VITREOMACULAR TRACTION TREATED WITH A SINGLE INTRAVITREAL INJECTION OF OCRIPLASMIN.

PURPOSE: To report long-term outcomes in patients with vitreomacular traction injected with intravitreal ocriplasmin. METHODS: Interventional case series. PATIENTS: A 64-year-old woman and a 46-year-old woman. RESULTS: In Case 1, a 64-year-old woman with focal vitreomacular traction with impending macular hole presented with a visual acuity of 20/80 +1 and was injected with ocriplasmin 11 days later. Visual acuity continued to improve and stabilized through 60 weeks of follow-up with a final visual acuity of 20/50. Vitreomacular traction release was confirmed by optical coherence tomography 6 weeks after injection.In Case 2, a 46-year-old woman with focal vitreomacular traction presented with a visual acuity of 20/60 and received ocriplasmin treatment the same day. Vitreomacular traction release was confirmed by optical coherence tomography 2 days later. After subsequent worsening of visual acuity, pneumatic retinopexy and pars plana vitrectomy were performed. Visual acuity continued to improve and stabilize throughout the 52-week follow-up with a final visual acuity of 20/25. CONCLUSION: We present here two patients with focal vitreomacular traction treated with ocriplasmin and followed up long-term for up to one year. In both cases, visual acuity improved compared with baseline and stabilized after ocriplasmin treatment. These cases add to the growing literature demonstrating resolution of symptoms after ocriplasmin treatment over longer follow-up periods.

Long-term results of combination therapy using anti-VEGF agents and dexamethasone intravitreal implant for retinal vein occlusion: an investigational case series.

BACKGROUND: One limitation of anti-VEGF therapy is the need for monthly retreatment to maintain efficacy. The purpose of this study was to determine the duration of effect in eyes with macular edema (ME) secondary to branch or central retinal vein occlusion (BRVO or CRVO) treated with anti-VEGF therapy plus sustained-release dexamethasone (DEX implant; Ozurdex). MATERIALS AND METHODS: This open-label, interventional case series included 62 eyes with ME due to RVO, central foveal thickness (CFT) >300 µm, and best-corrected visual acuity (BCVA) of 20/40 or worse. Each treatment cycle included an anti-VEGF injection followed 2 weeks later with DEX implant. Patients were eligible for retreatment if CFT increased to >290 µm or increased by >50 µm from the lowest measurement, or if BCVA decreased by six or more Snellen letters. Efficacy and safety were evaluated 2 and 4-6 weeks after the beginning of each treatment cycle and every 4 weeks thereafter until retreatment criteria were met. The primary outcome measure was time to retreatment. Secondary outcome measures included BCVA, CFT, and safety parameters. RESULTS: The mean reinjection interval for all patients was 135.5±36.4 days. There was no statistically significant difference in mean intertreatment interval for up to six cycles of treatment or between eyes with BRVO or CRVO (P≥0.058). Mean peak change in BCVA was 13.8 letters, and 47.6% of eyes gained three or more lines of BCVA. The mean peak decrease in CFT across all treatment cycles was 200.9 µm for eyes with BRVO and 219.2 µm for eyes with CRVO. The percentage of patients with CFT ≤300 µm at any time during a given treatment cycle ranged from 78% to 94% among eyes with BRVO and from 85% to 100% among eyes with CRVO. Intraocular pressure increased in 19 of 62 eyes, and 26 of 44 phakic eyes underwent cataract surgery. CONCLUSION: In eyes with ME due to RVO, treatment with an anti-VEGF agent plus DEX implant provided a predictable duration of effect, as well as significant improvements in BCVA and CFT.

Ultra-widefield Imaging of the Peripheral Retinal Vasculature in Normal Subjects.

PURPOSE: To establish the extent of the peripheral retinal vasculature in normal eyes using ultra-widefield (UWF) fluorescein angiography. DESIGN: Prospective, observational study. PARTICIPANTS: Fifty-nine eyes of 31 normal subjects, stratified by age, with no evidence of ocular disease in either eye by history and ophthalmoscopic examination. METHODS: Ultra-widefield fluorescein angiographic images were captured centrally and with peripheral steering using the Optos 200Tx (Optos, Dunfermline, United Kingdom). Images obtained at different gaze angles were montaged and corrected for peripheral distortion using a stereographic projection method to provide a single image for grading of the peripheral edge of the visible vasculature. The border of the vascularized retina was expressed as a radial surface distance from the center of the optic disc. The vascularized area was calculated based on this mean peripheral border position for each quadrant. MAIN OUTCOME MEASURES: Mean distance (mm) from the center of optic disc to the peripheral vascular border. RESULTS: In normal eyes, the mean radial surface distance from the center of the optic disc to the peripheral edge of the visible vasculature was 20.3±1.4 mm and the mean area of normal perfused retina was 977.0 mm(2). There was no significant difference between right and left eyes or between male and female participants. However, the distance to the periphery differed depending on the quadrant, with temporal (22.5±0.9 mm) being larger than inferior (20.4±1.7 mm) being larger than superior (19.2±1.5 mm) being larger than nasal (17.4±0.9 mm; P < 0.001) for all interquadrant comparisons. Interestingly, the distances to the perfused vascular border were significantly shorter in older individuals (≥60 years) than in younger subjects. CONCLUSIONS: Ultra-widefield fluorescein angiography is an important tool for studying the extent of peripheral retinal vasculature. With the increasing use of UWF imaging to evaluate and manage patients with retinal vascular disease, the normative data from this study may provide a useful reference when assessing the pathologic significance of findings in the setting of disease.

Measuring the precise area of peripheral retinal non-perfusion using ultra-widefield imaging and its correlation with the ischaemic index.

OBJECTIVE: To determine the calculated, anatomically correct, area of retinal non-perfusion and total area of visible retina on ultra-widefield fluorescein angiography (UWF FA) in retinal vein occlusion (RVO) and to compare the corrected measures of non-perfusion with the ischaemic index. METHODS: Uncorrected UWF FA images from 32 patients with RVO were graded manually for capillary non-perfusion, which was calculated as a percentage of the total visible retina (uncorrected ischaemic index). The annotated images were converted using novel stereographic projection software to calculate precise areas of non-perfusion in mm(2), which was compared as a percentage of the total area of visible retina ('corrected non-perfusion percentage') with the ischaemic index. RESULTS: The precise areas of peripheral non-perfusion ranged from 0 mm(2) to 365.4 mm(2) (mean 95.1 mm(2)), while the mean total visible retinal area was 697.0 mm(2). The mean corrected non-perfusion percentage was similar to the uncorrected ischaemic index (13.5% vs 14.8%, p=0.239). The corrected non-perfusion percentage correlated with uncorrected ischaemic index (R=0.978, p<0.001), but the difference in non-perfusion percentage between corrected and uncorrected metrics was as high as 14.8%. CONCLUSIONS: Using stereographic projection software, lesion areas on UWF images can be calculated in anatomically correct physical units (mm(2)). Eyes with RVO show large areas of peripheral retinal non-perfusion.

Area of peripheral retinal nonperfusion and treatment response in branch and central retinal vein occlusion.

PURPOSE: To evaluate the extent of peripheral retinal nonperfusion in retinal vein occlusion and to determine its effect on the severity of macular edema and response to treatment. METHODS: This prospective clinic-based cohort study included 32 consecutive patients with retinal vein occlusion and refractory macular edema evaluated using spectral domain optical coherence tomography and wide-field fluorescein angiography. Areas of ischemia were calculated as a percentage of the total visible retina (ischemic index), which was evaluated when macular edema was present (foveal central subfield >300 µm) and when edema had resolved (foveal central subfield ≤ 300 µm). Ischemic index was the main outcome measure. RESULTS: The mean ischemic index at study enrollment was 14.8% and was larger when macular edema was present compared with when edema had resolved (14.8 vs. 10.3%, P < 0.001). Compared with those with less nonperfusion, patients with ischemic index >10% had thicker mean foveal central subfield on optical coherence tomography (520.8 vs. 424.5 µm, P = 0.029) and worse visual acuity (56.3 vs. 59 letters) with the presence of macular edema and experienced greater decrease in optical coherence tomography (296.1 vs. 165.3 µm, P = 0.019) and gain in visual acuity (12.4 vs. 0.9 letters, P = 0.036) in response to treatment. CONCLUSION: The area of peripheral retinal nonperfusion is variable in patients with retinal vein occlusion and affects its clinical course and response to treatment.

Effect of combination therapy with bevacizumab and dexamethasone intravitreal implant in patients with retinal vein occlusion.

OBJECTIVE: The objective of this study was to determine if dexamethasone intravitreal implant 0.7 mg (Ozurdex; Allergan, Inc) with bevacizumab (Avastin; Genentech, Inc) therapy can be synergistic, providing further improvements in visual acuity, sustainability, and macular thickness when compared with dexamethasone intravitreal implant 0.7 mg alone. METHODS: This is a prospective, interventional case series intended to monitor changes in visual acuity and macular thickness in patients diagnosed with retinal vein occlusion (RVO), after injection of bevacizumab followed by a scheduled dexamethasone intravitreal implant. This study was designed to emulate patient care as received in the typical ophthalmology practice. Patients diagnosed with RVO, who were seen between September 2009 and July 2010, were included in this study if they had received previous anti-vascular endothelial growth factor therapy. Patients were included in analysis if the previous anti-vascular endothelial growth factor therapy was at least 6 weeks before and optical coherence tomography (OCT) was >300 µm on spectral-domain OCT. Exclusion criteria included history of vitrectomy, and/or rubeotic or advanced glaucoma. All patients were evaluated with Snellen visual acuity and measured for macular thickness (calculated by spectral-domain OCT) and intraocular pressure. At baseline, all patients were injected with bevacizumab, followed by dexamethasone intravitreal implant injection 2 weeks later. These patients were reexamined on a monthly basis and retreated when edema occurred. RESULTS: The primary outcome measure was the time to reinjection based on OCT and vision criteria. The secondary outcomes were increases in visual acuity and the reduction of OCT thickness during that period. Thirty-four eyes of 33 patients, with a mean age of 72.8 years, were identified. Thirty-five percent were diagnosed with central RVO, while the other 65% were with branch RVO. Of these patients, 97% gained vision during the study. Mean visual acuity improved from initially 11 letters to a maximum of 25 letters during the study period. In addition, vision improved by at least 15 letters in 29% of patients initially up to 64% during the study period. Macular thickness decreased with the combination treatment by OCT, and the effect continued an average of 126 days from the initial bevacizumab treatment. Retreatment was unnecessary in 18% of the population during the 6-month study period. CONCLUSION: This study demonstrates efficacy and the duration of effect using a combination of bevacizumab and dexamethasone versus dexamethasone alone. The combination is synergistic, increasing visual acuity and prolonging the time between injections, compared with either of these medications alone. Therefore, the combination of a vascular endothelial growth factor inhibitor and a dexamethasone implant may be a valuable option for RVO treatment.

Choroidal melanoma: natural history and management options.

BACKGROUND: Choroidal melanoma is the most common primary malignancy of the eye. Enucleation has been the mainstay of treatment, but new and more effective options have recently been proposed as eye- and vision-sparing alternatives. METHODS: We reviewed the medical literature for trials and case reports involving the evolution, current uses, and limitations of alternatives to enucleation for treating choroidal melanoma. RESULTS: Options to treat choroidal melanomas depend on the location and size of the tumor and goals of therapy. Local control with plaque radiotherapy has provided overall survival comparable to enucleation. Transscleral resection may leave behind potentially viable melanoma cells following surgery; adjuvant brachytherapy is recommended to irradiate remaining tumor cells. Elevating tissue temperature potentiates the effect of ionizing radiation, thus reducing the dose of radiation needed to treat uveal melanoma. Transpupillary thermotherapy has been effective only in select circumstances, and long-term results have shown poorer local control rates and similar visual outcomes compared with other conservative treatment methods. CONCLUSIONS: Treatment therapies for choroidal melanoma warrant further study. Currently, enucleation remains as effective as the eye- and vision-sparing approaches.