Daniela Calucci

Intravitreal bevacizumab (Avastin) for persistent new vessels in diabetic retinopathy (IBEPE study).

Objective: To evaluate the short-term fluorescein angiographic and visual acuity effects of a single intravitreal injection of bevacizumab (Avastin) for the management of persistent new vessels (NV) associated with diabetic retinopathy. Methods: A prospective, nonrandomized open-label study of diabetic patients with actively leaking NV refractory to laser treatment and best-corrected Early Treatment Diabetic Retinopathy Study visual acuity (BCVA) worse than 20/40. Standardized ophthalmic evaluation was performed at baseline and at weeks 1, 6, and 12 (±1) following intravitreal injection of 1.5 mg of bevacizumab. Main outcome measures include changes in total area of fluorescein leakage from active NV and BCVA. Results: Fifteen consecutive patients (men, 9 [60%]; women, 6 [40%]) were included and all completed the 12-week follow-up period of the study. The mean ± SD age of participants was 60.08 ± 7.75 years (median, 59.5; range, 49–73 years). At baseline, mean ± standard error of the mean (SEM) NV leakage area was 27.79 ± 6.29 mm2. The mean ± SEM area of active leaking NV decreased significantly to 5.43 ± 2.18 mm2 and 5.50 ± 1.24 mm2 (P < 0.05, Tukey multiple comparisons post-test) at 1 and 12 weeks postinjection, respectively; at week 6 no leakage was observed. The mean ± SEM logMAR (Snellen equivalent) BCVA improved significantly from 0.90 (20/160) ± 0.11 at baseline to 0.76 (20/125+2) ± 0.12, 0.77 (20/125+2) ± 0.11, and 0.77 (20/125+2) ± 0.12 at weeks 1, 6, and 12, respectively (P < 0.05, Tukey multiple comparisons post-test). No major adverse events were observed. Conclusions: Intravitreal injection of bevacizumab achieved short-term reduction of fluorescein leakage from persistent active NV without loss of vision in patients with diabetic retinopathy. Further studies to investigate the role of anti-VEGF therapy with bevacizumab for the management of diabetic retinopathy refractory to laser treatment are warranted.

Retinal assessment using optical coherence tomography

Over the 15 years since the original description, optical coherence tomography (OCT) has become one of the key diagnostic technologies in the ophthalmic subspecialty areas of retinal diseases and glaucoma. The reason for the widespread adoption of this technology originates from at least two properties of the OCT results: on the one hand, the results are accessible to the non-specialist where microscopic retinal abnormalities are grossly and easily noticeable; on the other hand, results are reproducible and exceedingly quantitative in the hands of the specialist. However, as in any other imaging technique in ophthalmology, some artifacts are expected to occur. Understanding of the basic principles of image acquisition and data processing as well as recognition of OCT limitations are crucial issues to using this equipment with cleverness. Herein, we took a brief look in the past of OCT and have explained the key basic physical principles of this imaging technology. In addition, each of the several steps encompassing a third generation OCT evaluation of retinal tissues has been addressed in details. A comprehensive explanation about next generation OCT systems has also been provided and, to conclude, we have commented on the future directions of this exceptional technique.

Intravitreal bevacizumab (avastin) for central and hemicentral retinal vein occlusions: IBeVO study.

Purpose: To evaluate the safety, visual acuity changes, and morphologic effects associated with intravitreal bevacizumab injections for the management of macular edema due to ischemic central or hemicentral retinal vein occlusion (RVO). Methods: In this prospective, open-label study, 7 consecutive patients (7 eyes) with macular edema associated with ischemic central or hemicentral RVO were treated with intravitreal injections of 2.0 mg (0.08 mL) of bevacizumab at 12-week intervals. Standardized ophthalmic evaluation was performed at baseline and at weeks 1, 6, and 12 after each injection. Clinical evidence of toxicity and complications as well as changes in logarithm of minimum angle of resolution Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), central macular thickness (CMT) and total macular volume (TMV) shown by optical coherence tomography (OCT), and dye leakage shown by fluorescein angiography were evaluated. Results: The median age of the 7 patients was 65 years (range, 58–74 years), and the median duration of symptoms before injection was 7 months (range, 2.5–16 months). At baseline, mean BCVA was 1.21 (Snellen equivalent, ≈20/320) in the affected eye. Mean baseline CMT and TMV were 730.1 &mgr;m and 17.1 mm3, respectively. Fluorescein leakage was observed in the macula and affected retinal quadrants in all seven eyes. Six patients completed the 25-week follow-up examination with reinjections performed at weeks 12 and 24. The most common adverse events were conjunctival hyperemia and subconjunctival hemorrhage at the injection site. At the last follow-up, mean BCVA in the affected eye was 0.68 (Snellen equivalent, 20/100+1). No patient had a decrease in BCVA. Mean CMT and TMV at the 25-week follow-up were 260.3 &mgr;m and 9.0 mm3, respectively; fluorescein leakage within the macula and affected retinal quadrants as compared with baseline was markedly reduced in all patients. Coupled with fluorescein angiographic findings, OCT data suggest a trend of macular edema recurrence between 6 weeks and 12 weeks after injection. Conclusions: Intravitreal bevacizumab injections of 2.0 mg at 12-week intervals were well tolerated and were associated with short-term BCVA stabilization or improvement and favorable macular changes in all patients with ischemic RVO and associated macular edema.

Immediate indocyanine green angiography and optical coherence tomography evaluation after photodynamic therapy for subfoveal choroidal neovascularization.

Purpose To better understand the mechanisms of action of photodynamic therapy (PDT) with verteporfin for subfoveal choroidal neovascularization (CNV), the authors evaluated the retinal and choroidal response immediately after treatment with serial optical coherence tomography (OCT) and indocyanine green angiography (ICGA). Methods This study was a prospective, noncomparative case series. PDT was performed on nine eyes of nine consecutive patients who presented with subfoveal CNV due to age-related macular degeneration, and serial evaluation with OCT as well as ICGA was performed at 20-minute intervals for the first 2 hours and then at 1 week, 1 month, and 3 months. Results In the first 2 hours after PDT, OCT showed an increase in the thickness of the retina in the treatment area due to fluid leakage from the neovascular complex as confirmed by ICGA. At 1 week, marked reduction of intraretinal/subretinal fluid was observed in all patients. Neovascular complex nonperfusion by ICGA was associated with some degree of choroidal hypoperfusion in the treatment area. Return of the foveal contour by OCT was optimal after 1 month of treatment. At 3 months, choroidal reperfusion by ICGA and recurrent intraretinal/subretinal fluid by OCT were observed. Conclusions Serial OCT and ICGA evaluation after PDT suggests that the initial successful CNV nonperfusion as shown by fluorescein angiography at 1 week occurs by means of selective PDT damage to the lesion and/or reduced choroidal blood flow in the treatment area, thereby decreasing intraretinal/subretinal fluid and facilitating restoration of the retinal architecture.

Indocyanine green-mediated photothrombosis as a new technique of treatment for persistent central serous chorioretinopathy

Purpose. To evaluate the potential benefit and complications of indocyanine green-mediated photothrombosis (IMP) in the management of patients with persistent central serous chorioretinopathy (CSC). Methods. Interventional noncomparative case series. Eleven patients with CSC presenting with persistent subretinal fluid in optical coherence tomography (OCT) four months after presentation and decrease in visual acuity (VA) were submitted to a single IMP session with 2 mg/kg body weight ICG and application of 5.6 W/cm 2 light at 810 nm. A continuous follow-up was provided with best-corrected ETDRS VA assessment, and angiographic and OCT documentation 72 hours before and at 2 days, 1 and 2 weeks, 1, 3, 6, and 12 months after treatment. Results. Pretreatment VA levels ranged from 20/32 - 1 to 20/100 (mean, 20/63 + 2 [logMAR equivalent, 0.460 ±0.155]); post treatment levels ranged from 20/25 - 2 to 20/20 (mean, 20/20 - 2 [logMAR equivalent, 0.038 ± 0.048]). Ten out of eleven patients presented with VA levels of =20/25 2 weeks after treatment; the mean logMAR VA change of 0.345 at that time was statistically significant (p < 0.05, Friedman test). OCT disclosed resolution of persistent subretinal fluid in all eyes. No recurrence was observed after 12 months of follow-up. Complications included transient retinal whitening in two patients, and associated occlusion of retinal capillaries in one. Conclusions. Photothrombosis using low-intensity 810 nm light to direct laser energy continuously at the active leakage sites after intravenous ICG infusion induced rapid VA recovery in patients with persistent CSC; accordingly, restoration of the macular architecture was evidenced on OCT, and no recurrence was noted 12 months after IMP.

Multimodal fundus imaging in Best vitelliform macular dystrophy.

BackgroundBest vitelliform macular dystrophy (BVMD) is a rare autosomal dominant retinal disease of highly variable phenotypic expression. Interpretations of disease mechanisms based on histopathology, electrophysiology, genetic analysis, and retinal imaging are somewhat discordant in fundamental issues such as the location and extension of primary retinal changes. Herein we describe the morphological macular features in patients with BVMD undergoing simultaneous multimodal fundus imaging and compare to those of normal age-matched subjects.MethodsComparative study including seven patients with BVMD (14 eyes) and seven age-matched healthy subjects (14 eyes). All participants were submitted to complete ophthalmological examination, fundus photography, and standardized multimodal fundus imaging protocol including Fourier-domain optical coherence tomography (Fd-OCT) combined with near-infrared reflectance and blue-light fundus autofluorescence (FAF).ResultsIn two eyes in the “subclinical” stage, Fd-OCT revealed thickening of the middle highly reflective layer (HRL) localized between the photoreceptors’ inner/outer segments junction (inner-HRL) and RPE/Bruch’s membrane reflective complex (outer-HRL) throughout the macula. In one eye in the “vitelliform” stage, a homogeneous hyper-reflective material on Fd-OCT was observed between the middle-HRL and outer-HRL; this material presented increased fluorescence on FAF. The outer nuclear layer (ONL) was thinned in the central macula and subretinal fluid was not identified in these earlier disease stages. In patients of “pseudohypopyon” (two eyes), “vitelliruptive” (eight eyes) and “atrophic” (one eye) stages, Fd-OCT revealed a variety of changes in the middle- and inner-HRLs and thinning of ONL. These changes were found to be associated with the level of visual acuity observed. Thickening of the middle-HRL was observed beyond the limits of the clinically evident macular lesion in all eyes.ConclusionsMultimodal fundus imaging demonstrated thickening of the reflective layer corresponding to the photoreceptors’ outer segments throughout the macula with no subretinal fluid accumulation as the earliest detectable feature in BVMD. Changes detected in the photoreceptors’ reflective layers (middle- and inner- HRLs) and ONL thinning seemed to be progressive with direct implications for the level of visual acuity impairment observed among the different stages of the disease.

Spectral optical coherence tomography findings in patients with ocular toxoplasmosis and active satellite lesions (MINAS Report 1)

Purpose:  To characterize the active retinochoroiditis lesion observed in patients with the classic clinical presentation of ocular toxoplasmosis (OT) utilizing spectral optical coherence tomography (SOCT).

OCT findings in macular hole formation in eyes with complete vitreofoveal separation.

The current study describes the morphologic macular features in two eyes that developed full-thickness macular holes in the setting of documented vitreofoveal separation. Using third-generation optical coherence tomography, complete vitreofoveal separation associated with the disruption of the inner foveal retina was documented in both cases. Five months after presentation, decreased vision and epiretinal membrane formation associated with development of a full-thickness macular hole were observed in the first patient. In the second patient, a full-thickness macular hole was demonstrated by optical coherence tomography 6 weeks after presentation. These findings suggest that full-thickness macular holes may develop in eyes with vitreofoveal separation. Evidence of the disturbance of the inner foveal architecture on optical coherence tomography indicates the potential role of factors other than anteroposterior or oblique vitreoretinal tractional forces in the genesis of some full-thickness macular holes.

Intravitreal bevacizumab (Avastin) for persistent new vessels in diabetic retinopathy (IBEPE study): 1-year results.

Purpose: To evaluate the effect of intravitreal bevacizumab on area of fluorescein leakage from active new vessels (NVs) and on best-corrected visual acuity in patients with actively leaking NV associated with diabetic retinopathy unresponsive to panretinal photocoagulation. Methods: A prospective open-label study of diabetic patients with actively leaking NV refractory to panretinal photocoagulation and best-corrected visual acuity worse than 20/40. Ophthalmic evaluation, including fluorescein angiography, was performed at baseline and at Weeks 1, 6, 12, 24, and 48 after intravitreal bevacizumab (1.5 mg/0.06 mL) injection. After Week 12, patients could receive additional intravitreal bevacizumab injections pro re nata, per the discretion of the treating ophthalmologist. Main outcome measures include change from baseline (at each study visit) in total area of fluorescein leakage from active NV and change from baseline in best-corrected visual acuity. Results: Fifteen consecutive patients were included, and 12 completed the study. Mean ± SEM fluorescein leakage was 27.7 ± 6.2 mm2 at baseline and was significantly lower at all visits post injection; at Week 6, no leakage was observed (P = 0.0001). The mean ± SEM logarithm of minimum angle of resolution best-corrected visual acuity improved from 0.90 ± 0.11 at baseline to 0.70 ± 0.12 at Week 48 (P = 0.0449). Throughout the 48-week study period, patients received a mean of 2.16 injections. Conclusion: With 1-year follow-up, treatment with intravitreal bevacizumab was associated with reduced fluorescein leakage from persistent NV and improved visual acuity in patients with diabetic retinopathy unresponsive to panretinal photocoagulation.

Proposed physiopathological mechanisms and potential therapeutic targets for central serous chorioretinopathy

Central serous chorioretinopathy manifests as idiopathic serous detachment of the neurosensory retina, occasionally associated with small retinal pigment epithelium detachments in the macular area. The actual pathobiological mechanisms are not completely understood, but a strong association with endogenous or exogenous hypercortisolism is presumed. Although the clinical presentation may vary widely, visual symptoms are generally mild, unspecific and transitory. In rare circumstances the condition can evolve to significant and permanent visual impairment related to severe manifestations, relapsing or chronic episodes and secondary complications. Symptoms tend to resolve spontaneously in 3–6 months, but recurrences are expected to occur in up to 50% of the cases. Ancillary examinations may assist the diagnosis and identification of associated complications. While focal leaks at the level of the retinal pigment epithelium are highlighted on fluorescein angiography, indocyanine green angiography reveals widespread fundus involvement with multiple regions of choroidal hyperpermeability. Several therapeutic approaches have been proposed in unfavorable (persistent central serous chorioretinopathy) cases. In this article the proposed physiopathological mechanisms are discussed, leading to new insights into the clinical diagnosis and multidisciplinary management of this somewhat paradoxal disease.