Jose A. Cardillo

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.

Randomized Clinical Trial Evaluating mETDRS versus Normal or High-Density Micropulse Photocoagulation for Diabetic Macular Edema

PURPOSE To compare modified Early Treatment Diabetic Retinopathy Study (mETDRS) focal/grid laser photocoagulation with normal-density (ND-SDM) or high-density (HD-SDM) subthreshold diode-laser micropulse photocoagulation for the treatment diabetic macular edema (DME). METHODS A prospective, randomized, controlled, double-masked clinical trial with patients with previously untreated DME and best corrected visual acuity (BCVA) worse than 20/40 and better than 20/400. Patients were randomized to receive either mETDRS focal/grid photocoagulation (42 patients), ND-SDM (39 patients), or HD-SDM (42 patients). Before treatment and 1, 3, 6, and 12 months after treatment, all patients underwent ophthalmic examinations, BCVA, color fundus photography, fluorescein angiography, and optical coherence tomography (OCT). RESULTS At 12 months, the HD-SDM group had the best improvement in BCVA (0.25 logMAR), followed by the mETDRS group (0.08 logMAR), whereas no improvements were seen in the ND-SDM group (0.03 logMAR). All groups showed statistically significant progressive reduction of central macular thickness (CMT) throughout the study (P < 0.001). The HD-SDM group exhibited the greatest CMT reduction (154 μm), which was not significantly different from that of the mETDRS group (126 μm; P = 0.75). CONCLUSIONS At 1 year, the clinical performance of HD-SDM was superior to that of the mETDRS photocoagulation technique, according to the anatomic and functional measures of improvement used in this investigation. A rationale for this treatment modality as a preferable approach is suggested, and the precise role of subthreshold micropulse laser treatment may become more defined as experience grows, guided by optimized treatment guidelines and more comprehensive trials. (Clinicaltrials.gov number, NCT00552435.).

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.

Photodynamic therapy with indocyanine green for occult subfoveal choroidal neovascularization caused by age-related macular degeneration

Purpose. To report two cases of occult subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) that were successfully treated utilizing large spot, low irradiance 810-nm light and intravenous injection of small-volume, high-concentration indocyanine green (ICG) bolus, termed ICG-mediated photodynamic therapy (i -PDT). Methods. Case report. Two patients with occult subfoveal CNV (two eyes) due to AMD were treated with i -PDT and were prospectively followed with fluorescein and indocyanine green angiography as well as optical coherence tomography (OCT). Results. Both patients presented a 3-line increase in visual acuity by twelve months of follow-up. A significant regression of the CNV was demonstrated by fluorescein angiography within one week following treatment. OCT revealed diminishing of the subretinal fluid. There were no complications related to the procedure. Conclusion. i -PDT induced CNV regression and improved the visual acuity in these particular cases, suggesting a new and promising way to treat neovascular AMD. The partial anatomical restoration associated to the improvement of the visual function observed in both patients suggests that a selective therapeutic effect was achieved. Further studies are required not only to assess the clinical value of this treatment but also to better understand the major mechanism of action involving this novel treatment modality.

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.

A prospective randomized trial of intravitreal bevacizumab versus ranibizumab for the management of diabetic macular edema.

PURPOSE To compare visual acuity and spectral-domain optical coherence tomography (SDOCT) outcomes associated with intravitreal (IV) bevacizumab vs IV ranibizumab for the management of diabetic macular edema (DME). DESIGN Prospective randomized trial. METHODS Forty-eight patients (63 eyes) with center-involved DME were randomly assigned to receive 1.5 mg (0.06 cc) IV bevacizumab or 0.5 mg (0.05 cc) IV ranibizumab at baseline and monthly if central subfield thickness was greater than 275 μm. RESULTS Forty-five patients (60 eyes) completed 48 weeks of follow-up. At baseline, mean ± standard error best-corrected visual acuity (BCVA) (logMAR) was 0.60 (20/80) ± 0.05 in the IV bevacizumab group and 0.63 (20/85) ± 0.05 in the IV ranibizumab group. A significant improvement in mean BCVA was observed in both groups at all study visits (P < .05); this improvement was significantly greater in the IV ranibizumab group compared with the IV bevacizumab group at weeks 8 (P = .032) and 32 (P = .042). A significant reduction in mean central subfield thickness was observed in both groups at all study visits compared with baseline (P < .05), with no significant difference in the magnitude of macular thickness reduction between groups. The mean number of injections was significantly higher (P = .005) in the IV bevacizumab group (9.84) than in the IV ranibizumab group (7.67). CONCLUSIONS IV bevacizumab and IV ranibizumab are associated with similar effects on central subfield thickness in patients with DME through 1 year of follow-up. IV ranibizumab is associated with greater improvement in BCVA at some study visits, and the mean number of injections is higher in the IV bevacizumab group.

Clinical applications of the sustained-release dexamethasone implant for treatment of macular edema

Macular edema is one of the leading causes of vision loss among patients with retinal vein occlusion, diabetic retinopathy, and posterior chamber inflammatory disease. However, the treatment of macular edema is considerably limited by the difficulty in delivering effective doses of therapeutic agents into the vitreous cavity. In recent years, the development of a sustained-release dexamethasone intravitreal implant (Ozurdex®) has enabled more controlled drug release at a stable rate over a long period of time, with a potentially lower rate of adverse events. Clinical studies indicate that this dexamethasone implant is a promising new treatment option for patients with persistent macular edema resulting from retinal vein occlusion, diabetic retinopathy, and uveitis or Irvine-Gass syndrome.