Thanos D. Papakostas

Intravitreal ranibizumab, intravitreal ranibizumab with PDT, and intravitreal triamcinolone with PDT for the treatment of retinal angiomatous proliferation: a prospective study.

Purpose: To compare 1) intravitreal ranibizumab, 2) intravitreal ranibizumab plus photodynamic therapy (PDT), and 3) intravitreal triamcinolone plus PDT in retinal angiomatous proliferation. Methods: In this prospective study, 37 eyes of 37 patients with retinal angiomatous proliferation were randomly assigned in 1 of the 3 groups. The patients in Group 1 (n = 13) received 3 monthly injections of 0.5 mg of ranibizumab. The patients in Group 2 (n = 13) received one session of PDT and 3 monthly intravitreal injections of 0.5 mg ranibizumab and the patients in Group 3 (n = 11) received one session of PDT and 1 injection of 4 mg triamcinolone. Retreatment, with the same therapeutic scheme in each group, was considered in case of persistence or recurrence of subretinal fluid or intraretinal fluid. Results: All the patients completed at least 6 months of follow-up. A total of 61.53% patients in Group 1, 76.92% in Group 2, and all in Group 3 had the same or better visual acuity at the end of the follow-up (P = 0.0232). The mean central retinal thickness reduction in Group 1 was 32.23 &mgr;m (P = 0.548), in Group 2 20.31 &mgr;m (P = 0.042), and in Group 3 73.92 &mgr;m (P < 0.0001). Also, the patients in Group 3 received on average the lowest number of injections (P < 0.0001). Conclusion: All groups resulted in stabilization of the disease, while a significant trend towards better visual acuity and anatomic restoration of the affected area was observed in the intravitreal triamcinolone & PDT group.

Photodynamic Therapy, Ranibizumab, And Ranibizumab With Photodynamic Therapy For The Treatment Of Polypoidal Choroidal Vasculopathy

Purpose: The purpose of this study was to compare photodynamic therapy (PDT), ranibizumab, and ranibizumab with PDT in polypoidal choroidal vasculopathy. Methods: In this retrospective comparative study, 30 eyes of 30 patients with polypoidal choroidal vasculopathy were assigned to 1 of the 3 groups. The patients in Group 1 (n = 11) received 1 session of PDT. The patients in Group 2 (n = 10) received 3 monthly intravitreal injections of 0.5 mg ranibizumab, and the patients in Group 3 (n = 9) received 1 session of PDT and 3 injections of 0.5 mg ranibizumab. Retreatment, with the same therapeutic scheme in each group, was considered in case of leaking polyps on the indocyanine green angiography in Groups 1 and 3 and persistence or recurrence of subretinal fluid, intraretinal fluid, and/or hemorrhages in Group 2. Results: All the patients completed 12 months of follow-up. The visual acuity in the patients of Group 1 improved by 0.25 logarithm of the minimum angle of resolution units (P < 0.001), whereas the differences in the visual acuity in the other 2 groups were not statistically significant (0.04 logarithm of the minimum angle of resolution, P = 0.8118 in Group 2 and 0.18 logarithm of the minimum angle of resolution, P > 0.05 in Group 3). Of the patients in Group 1, 45.45% gained more than 3 lines (P = 0.0056), whereas no patient in Groups 2 and 3 experienced such a difference. No patient in Group 1 and 11.1% (n = 1) in Group 3 had angiographically evident polyps at 12 months, whereas 90% (n = 9) of the patients in Group 2 had persistent leakage. No extensive submacular hemorrhage or other complications were noted during the follow-up period. Conclusion: Photodynamic therapy resulted in a significantly better outcome at the end of the follow-up, whereas the patients who received ranibizumab or PDT and ranibizumab experienced a stabilization of the disease.

Intravitreal bevacizumab combined with photodynamic therapy for the treatment of occult choroidal neovascularization associated with serous pigment epithelium detachment in age-related macular degeneration.

Purpose: To evaluate the efficacy of intravitreal injection of bevacizumab combined with photodynamic therapy (PDT) for the treatment of occult choroidal neovascularization (CNV) associated with serous pigment epithelium detachment (s-PED) due to age-related macular degeneration (AMD). Methods: In this retrospective study, six patients (six eyes) with subfoveal occult CNV associated with s-PED due to AMD were treated with intravitreal bevacizumab combined with PDT. All patients were treated at baseline with PDT followed by intravitreal bevacizumab 1.25 mg 1 hour later. Afterwards, according to the findings of optical coherence tomography and fluorescein angiography, repeat bevacizumab injections were given, if necessary, monthly for three doses followed by further doses every 3 months. PDT was repeated every 3 months according to the same criteria. Follow-up time was 9 months. Results: All patients completed their treatment during the first 3 months from baseline. Best-corrected visual acuity (BCVA) improved or remained stable related to the baseline values in all patients at the end of the follow-up time. Mean BCVA improved from 20/67 to 20/42. S-PED and subretinal fluid decreased or disappeared. The mean central 1-mm retinal thickness was reduced from baseline value for the 9-month follow-up period by 128 &mgr;m. Conclusion: Intravitreal bevacizumab combined with PDT seems to be a promising treatment with good functional and anatomical results for occult CNV associated with s-PED due to AMD.

Conversion to aflibercept for diabetic macular edema unresponsive to ranibizumab or bevacizumab

Background The purpose of this study was to determine if eyes with diabetic macular edema (DME) unresponsive to ranibizumab or bevacizumab would benefit from conversion to aflibercept. Methods This study was conducted as a retrospective chart review of subjects with DME unresponsive to ranibizumab and/or bevacizumab and subsequently converted to aflibercept. Results In total, 21 eyes from 19 subjects of mean age 62±15 years were included. The majority of subjects were male (63%). The median number of ranibizumab or bevacizumab injections before switching to aflibercept was six, and the median number of aflibercept injections after switching was three. Median follow-up was 5 months after the switch. Mean central foveal thickness (CFT) was 453.52±143.39 mm immediately prior to the switch. Morphologically, intraretinal cysts were present in all cases. Mean CFT after the first injection decreased significantly to 362.57±92.82 mm (Wilcoxon signed-rank test; P<0.001). At the end of follow-up, the mean CFT was 324.17±98.76 mm (P<0.001). Mean visual acuity was 0.42±0.23 logMAR just prior to the switch, 0.39±0.31 logMAR after one aflibercept injection, and 0.37±0.22 log-MAR at the end of follow-up. The final visual acuity was significantly better than visual acuity before the switch (P=0.04). Conclusion Eyes with DME unresponsive to multiple ranibizumab/bevacizumab injections demonstrate anatomical and visual improvement on conversion to aflibercept.

Angiographic and OCT features of retinal angiomatous proliferation.

BackgroundTo propose a classification system for retinal angiomatous proliferation (RAP) on the basis of the indocyanine green angiography (ICG).MethodsRetrospective chart review of 55 eyes of 55 patients presenting with RAP. Fluorescein angiography (FA), ICG and optical coherence tomography (OCT) were used to evaluate the patients.ResultsAll RAP lesions appeared as occult or minimally classic CNV on FA without clear evidence of pigment epithelium detachment (PED). We were able to identify five different patterns of RAP on the basis of ICG. These were focal (27.2%), irregular (21.8%), circular (21.8%), multifocal (18.2%), and combined (10.9%) hyperfluorescence. The sudden termination of retinal vessel course sign was observed in 14 of 55 eyes (25.4%), which had a circular or irregular pattern on the ICG. Only the circular RAP exhibited a late hypofluorescence (‘wash out’) with staining of the surrounding tissue on the ICG. Forty eight of 55 eyes (86%) had PED according to the OCT. Out of these 48 eyes, 19 had intraretinal fluid (IRF) alone, and the rest had IRF and subretinal fluid. The eight eyes (14%) without PED belonged to the focal hyperfluorescence group and the fluid was located intraretinally in cystic spaces. In addition, in four eyes (7%) with coexisting CNV a band of tissue beneath the RAP protruding in the PED was observed.ConclusionWe propose a classification system for RAP on the basis of ICG and present the angiographic and OCT findings of these lesions. These data may further aid in the early diagnosis of RAP and can be also used for prognosis and clinical course documentation.

Intravitreal aflibercept for macular oedema secondary to central retinal vein occlusion in patients with prior treatment with bevacizumab or ranibizumab.

PurposeTo report the visual and anatomic outcomes in eyes with macular oedema (MO) secondary to central retinal vein occlusion (CRVO) that were switched from either intravitreal bevacizumab or ranibizumab to intravitreal aflibercept.MethodsTwo-center retrospective chart review. Eyes with MO secondary to CRVO that received a minimum of three intravitreal injections of bevacizumab or ranibizumab and were switched to intravitreal aflibercept for persistent or recurrent MO not responding to either bevacizumab and/or ranibizumab.ResultsIn all 42 eyes of 42 patients were included in the study. The median visual acuity before the switch was 20/126, 1 month after the first injection of aflibercept 20/89 (P=0.0191), and at the end of the follow-up 20/100 (P=0.2724). The median CRT before the switch was 536 μm, 1 month after the first injection of aflibercept 293.5 μm (P=0.0038), and at the end of the follow-up 279 μm (P=0.0013 compared to before the switch). The median number of weeks between injections before the switch was 5.6 and after the switch was 7.6 (P<0.0001).ConclusionConverting eyes with refractory MO due to CRVO to aflibercept can result in stabilization of the vision, improved macular anatomy, and extension of the injection interval.

Intravitreal ranibizumab in a patient with choroidal neovascularization secondary to multiple evanescent white dot syndrome

Purpose To report the effect of a single intravitreal injection of ranibizumab in a patient with choroidal neovascularization (CNV) secondary to multiple evanescent white dot syndrome (MEWDS). Methods A 65-year-old woman with visual acuity (VA) 20/40, mild vitreous inflammation, optic disc edema, and white deep retinal round lesions in the right eye underwent fluorescein angiography, indocyanine green angiography, and optical coherence tomography. The diagnosis of MEWDS with peripapillary CNV was made and a single injection of ranibizumab (0.5 mg) was administered. Results At the 6-month follow-up visit, the VA in the right eye was 20/20, the CNV completely regressed, and the MEWDS findings disappeared. Conclusions Intravitreal ranibizumab appears to be a safe and effective treatment option in cases of CNV secondary to MEWDS, resulting in fast resolution of the macular edema and regression of the CNV. On the other hand, it is unclear whether the administration of ranibizumab contributed to a prompt regression of MEWDS.

A Novel Nonradioactive Method to Evaluate Vascular Barrier Breakdown and Leakage

PURPOSE To identify a novel, sensitive, nonradioactive leakage assay that can be used in the assessment of retinal vascular permeability in rats and mice. METHODS Breakdown of the vascular barrier was induced by vascular endothelial growth factor (VEGF), lipopolysaccharide (LPS), or diabetes. Biotinylated bovine serum albumin (bBSA) was administered as a tracer. After perfusion with lactated Ringers solution, extravasated bBSA was detected with immunoprecipitation and Western blot analysis or sandwich ELISA. The results were then normalized against the final bBSA plasma concentration, the circulation time, and the protein concentration of the tissue. RESULTS Six hours after VEGF injection, BRB breakdown was quantified in the injected eye and was 2.5-fold higher than in the contralateral phosphate-buffered saline (PBS)-injected eye (n = 6 rats, P < 0.01). Intravitreal LPS injection induced severe inflammation in the directly injected eye and moderate inflammation in the contralateral untreated eye. Leakage was six- and threefold higher, respectively, compared with that in the untreated control animals (n = 5 rats, P < 0.01). Nine-month diabetic rats had a threefold increase in vascular leakage compared with age-matched control animals (n = 6 retinas, P < 0.05). Twenty-four hours after intraperitoneal administration of LPS in mice, the animals showed increased vascular leakage in all tissue organs examined (retina, 1.7-fold; brain, 1.5-fold; and kidney, 1.3-fold). CONCLUSIONS bBSA can serve as an effective alternative to the current methods used for quantitating vascular leakage and especially the blood-retinal barrier breakdown. It is reasonably easy to perform, low in cost, and adaptable to experiments in mice.

Choroidal Changes Associated With Bruch Membrane Pathology in Pseudoxanthoma Elasticum

PURPOSE To investigate the impact of Bruch membrane pathology on the choroid in pseudoxanthoma elasticum (PXE). DESIGN Monocenter cross-sectional prospective case series. METHODS The study included 61 eyes of 51 patients with PXE and 54 eyes of 54 normal subjects. The diagnosis of PXE was based on skin biopsy, genetic analysis or both. Eyes with PXE were subdivided into 3 groups: eyes without choroidal neovascularization (CNV) or chorioretinal atrophy (Group 1); eyes with active or fibrotic CNV (Group 2); and eyes with chorioretinal atrophy only (Group 3). Choroidal thickness was measured using enhanced-depth imaging optical coherence tomography (EDI-OCT). RESULTS Compared to controls (331 μm ± 24; mean ± 95% CI), mean subfoveal choroidal thickness in eyes of patients with PXE was significantly reduced within all 3 groups (Group 1: 243 μm ± 29; Group 2: 184 μm ± 28; Group 3: 104 μm ± 28; P < 0.001). Associated structural changes included apparent loss of small choroidal vessels. The difference of PXE compared to control eyes was largest close to the optic disc and approximated the level of controls toward the periphery. Within the PXE subgroups, eyes without CNV or chorioretinal atrophy (Group 1) showed the least reduction of choroidal thickness, while it was most pronounced in Group 3. CONCLUSIONS The results indicate that changes of Bruch membrane can be associated with choroidal alterations, which are most pronounced in the presence of advanced disease. A role of Bruch membrane in choroidal homeostasis may reflect a possible contribution of Bruch membrane alterations to CNV and geographic atrophy development in age-related macular degeneration.

Complications of Emulsified Silicone Oil after Retinal Detachment Repair

Abstract Intraocular silicone oil has several important indications in vitreoretinal surgery, particularly the repair of complicated retinal detachments. Emulsification is a clinically significant complication of using silicone oil tamponade. There are several factors that can promote or prevent silicone oil emulsification after retinal detachment repair, including protein surfactants, contaminants, and shear forces. However, the duration of tamponade remains the most significant one. After emulsification has occurred, keratopathy and glaucoma are the most common complications. However, recent work has shown that emulsification can also affect the retina, optic nerve, and even extraocular structures. Limiting the amount of time the silicone oil remains in the eye is the most important factor in reducing its complications.