Rogério A. Costa

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.

Intravitreal triamcinolone versus bevacizumab for treatment of refractory diabetic macular oedema (IBEME study)

Background/aims: The aim of this study was to compare the morphological and visual acuity outcomes associated with a single intravitreal injection of triamcinolone acetonide versus bevacizumab for the treatment of refractory diffuse diabetic macular oedema. Methods: Twenty-eight patients were randomly assigned to receive a single intravitreal injection of either 4 mg/0.1 ml triamcinolone acetonide or 1.5 mg/0.06 ml bevacizumab. Comprehensive ophthalmic evaluation was performed at baseline and at weeks 1, 4, 8 (±1), 12 (±2) and 24 (±2) after treatment. Main outcome measures included central macular thickness measured with optical coherence tomography (OCT) and best corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity. Results: Twenty-six patients (26 eyes) completed all study visits (two patients missed two consecutive study visits). Central macular thickness was significantly reduced in the intravitreal triamcinolone group compared with the bevacizumab group at weeks 4, 8, 12 and 24 (p<0.05). Logarithm of the minimum angle of resolution (LogMAR) best-corrected visual acuity was significantly higher at weeks 8 (0.69; ∼20/100+1) and 12 (0.74; 20/100−2) in the intravitreal triamcinolone group compared with the bevacizumab group (weeks 8 (0.83; ∼20/125−1) and 12 (0.86; 20/160+2)) (p<0.05). Significant change from baseline in mean intraocular pressure (mmHg) was seen at week 4 (+2.25) only in the intravitreal triamcinolone group (p<0.0001). No patient had observed cataract progression during the study. Conclusions: One single intravitreal injection of triamcinolone may offer certain advantages over bevacizumab in the short-term management of refractory diabetic macular oedema, specifically with regard to changes in central macular thickness. The actual clinical relevance of our preliminary findings, however, remains to be determined in future larger studies.

Panretinal photocoagulation versus PRP plus intravitreal bevacizumab for high-risk proliferative diabetic retinopathy (IBeHi study)

Purpose:  To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal bevacizumab on best corrected visual acuity (BCVA) and total area of fluorescein leakage from active new vessels (NVs) in patients with high‐risk proliferative diabetic retinopathy (PDR).

Comparison of two doses of intravitreal bevacizumab (Avastin) for treatment of macular edema secondary to branch retinal vein occlusion: results from the Pan-American Collaborative Retina Study Group at 6 months of follow-up.

Purpose: To report the 6-month anatomical and visual outcomes after injecting two different doses of intravitreal bevacizumab in patients with macular edema secondary to branch retinal vein occlusion (BRVO). Methods: An interventional, retrospective multicenter study of 45 eyes that were treated with at least one intravitreal injection (24 eyes, 1.25 mg; 21 eyes, 2.5 mg) of bevacizumab is reported. The main outcome measures were the central 1-mm macular thickness (CMT) and the change in ETDRS lines of best-corrected visual acuity (BCVA) at 6 months. Results: Forty-five eyes were injected on average 26.1 months (range, 3–86 months) after the diagnosis. The average follow-up was 35.2 weeks (range, 24–52 weeks). All patients completed at least 6 months of follow-up. In the 1.25-mg dose group, at 1 month, there was an average gain of 4.5 lines of BCVA; at 3 months, 5.1 lines of BCVA; and at 6 months, 5.1 lines of BCVA (P < 0.005). In the 2.5-mg dose group, at 1 month, there was an average gain of 2.3 lines of BCVA; at 3 months, 3.8 lines of BCVA; and at 6 months, 4.8 lines of BCVA (P = 0.05). In the 1.25-mg dose group, the mean CMT ± SD decreased from 461 ± 211 &mgr;m at baseline to 321 ± 152 &mgr;m at 1 month, 273 ± 99 &mgr;m at 3 months, and 277 ± 114 &mgr;m at 6 months (P = 0.0002). In the 2.5-mg group, the mean CMT ± SD decreased from 385 ± 168 &mgr;m at baseline to 279 ± 111 &mgr;m at 1 month, 249 ± 97 &mgr;m at 3 months, and 240 ± 93 &mgr;m at 6 months (P = 0.011). Conclusion: There were no statistically significant differences between the two dose groups with regard to the number of injections and anatomical and functional outcomes. Intravitreal injection of bevacizumab at doses up to 2.5 mg appears to be effective in improving BCVA and reducing CMT in BRVO in the short term. Multiple injections are needed in a large number of eyes for continued control of macular edema and preservation of visual acuity in the short term. Longer studies are needed to determine what role if any intravitreal injection of bevacizumab may play in the long-term treatment of this condition.

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.

Choriocapillaris photodynamic therapy using indocyanine green

PURPOSE To evaluate the potential of photodynamic therapy using indocyanine green for occlusion of choroidal neovascularization, the authors studied efficiency and collateral damage of photodynamic therapy-induced photothrombosis in the rabbit choriocapillary layer. METHODS Fundus photography, fluorescein angiography, and light and transmission electron microscopy were used to study the efficiency of photodynamic therapy-induced photothrombosis using indocyanine green as the photosensitizer, and to assess the resultant collateral damage. The delivery system consisted of a modified infrared diode laser tuned to 810 nm, near the maximum absorption peak of indocyanine green. RESULTS Choriocapillary occlusion was achieved at indocyanine green doses of 10 and 20 mg/kg and a radiant as low as 6.3 J/cm(2). When photodynamic therapy was performed with indocyanine green doses of 10 mg/kg, damage to the neural retina was minimal. Only inner photoreceptor segments showed degeneration, probably secondary to choroidal ischemia. Bruch membrane remained intact. Retinal pigment epithelium was invariably damaged, as seen with other photosensitizers. Temporary occlusion of large choroidal vessels occurred at both dye doses. CONCLUSIONS In this experimental study, photodynamic therapy using indocyanine green and 810-nm light irradiation produced endothelium-bound intraluminal photothrombosis, with preservation of the retinal architecture and minimal loss of visual cells. Membrane targetability, hydrophilic and fluorescent properties, and activation at 805 nm suggest indocyanine green as a potential photosensitizer for choroidal neovascularization. These combined considerations point toward further study of photodynamic therapy using indocyanine green for the treatment of choroidal vascular disease.

Intraoperative Bleeding during Vitrectomy for Diabetic Tractional Retinal Detachment With versus Without Preoperative Intravitreal Bevacizumab (IBeTra Study)

Aims: To compare the amount of intraoperative intraocular bleeding in patients with diabetes with macula-involving tractional retinal detachment (TRD) undergoing pars plana vitrectomy (PPV) with and without preoperative intravitreal bevacizumab (IVB) injection. Methods: An institutional study was carried out with consecutive patients with diabetic retinopathy and macula-involving TRD of recent (3 months) onset who were randomly assigned to PPV only (PPV group) or PPV combined with one IVB (1.5 mg/0.06 ml) injection 2 weeks prior to surgery (bevacizumab (BEV)/PPV group). All patients underwent 23-gauge PPV 3 weeks after baseline. The main outcome measure was erythrocyte count in the fluid retrieved from the vitrectomy cassette using a Neubauer counting chamber. Results: The study included 20 patients. The mean erythrocyte count was 14 865×103 (SD 19 332×103; median 4500×103) cells in the BEV/PPV group, and 176 240×103 (SD 108 375×103; median 166 600×103) cells in the PPV group. The mean erythrocyte count was significantly lower in the BEV/PPV group than in the PPV group (p<0.0001). No major adverse events were identified. Conclusion: Preoperative IVB injection was associated with reduced intraocular bleeding during 23-gauge PPV for diabetic macula-involving TRD. Further studies are needed to confirm our preliminary findings. Trial registration number: NCT00690768.

Primary intravitreal bevacizumab for subfoveal choroidal neovascularization in age-related macular degeneration: results of the Pan-American Collaborative Retina Study Group at 12 months follow-up.

Purpose: To report the 12-month anatomic and Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA) response after primary intravitreal bevacizumab (Avastin™, Genentech Inc., San Francisco, CA) (1.25 mg or 2.5 mg) in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration. Methods: Sixty-three eyes of 63 consecutive patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration, a mean age of 73.7 ± 7.5 years and a minimum of 12 months (mean 55.5 ± 6.2 weeks) of follow-up participated in this interventional retrospective multicenter case series in 7 centers from 6 countries. Patients were treated with at least 1 intravitreal injection of 1.25 mg or 2.5 mg of bevacizumab. Patients underwent Early Treatment Diabetic Retinopathy Study BCVA testing, ophthalmoscopic examination, optical coherence tomography, and fluorescein angiography at baseline and follow-up visits. Repeated measures analysis of variance was used to compare mean values. Results: The mean number of intravitreal bevacizumab injections per eye was 3.5 (range, 1–8). Mean baseline BCVA was 20/320, logarithm of the minimum angle of resolution = 1.2, and mean final BCVA was 20/200, logarithm of the minimum angle of resolution = 1.0 (P < 0.001). Central macular thickness at baseline by optical coherence tomography had a mean of 389.2 ± 149.6 &mgr;m which was significantly reduced to a mean of 281.0 ± 96.1 &mgr;m, 268.2 ± 82.6 &mgr;m, 262.6 ± 92.3 &mgr;m, and 241.3 ± 76.7 &mgr;m at 1, 3, 6, and 12 months after initial treatment, respectively (P < 0.0001). Ocular adverse events included transient increased intraocular pressure in 2 (3.1%) eyes, endophthalmitis in 2 (3.1%) eyes, and transient hypotony in 1 eye (1.1%). No systemic adverse events were observed. Conclusion: Primary intravitreal bevacizumab at doses of 1.25 mg or 2.5 mg seems to provide stability or improvement in BCVA, optical coherence tomography, and fluorescein angiography in subfoveal choroidal neovascularization secondary to age-related macular degeneration at 12 months.