Francisco J. Rodriguez

Primary intravitreal bevacizumab for diffuse diabetic macular edema: the Pan-American Collaborative Retina Study Group at 24 months.

PURPOSE To report the 24-month anatomic and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) response after primary intravitreal bevacizumab (Avastin; Genentech, Inc., San Francisco, CA; 1.25 or 2.5 mg) in patients with diffuse diabetic macular edema (DDME). In addition, a comparison of the 2 different doses of intravitreal bevacizumab (IVB) used is presented. DESIGN Retrospective, multicenter, interventional, comparative case series. PARTICIPANTS The clinical records of 115 consecutive patients (139 eyes) with DDME at 11 centers from 8 countries were reviewed. METHODS Patients were treated with at least 1 intravitreal injection of 1.25 or 2.5 mg of bevacizumab. All patients were followed up for 24 months. Patients underwent ETDRS BCVA testing, ophthalmoscopic examination, optical coherence tomography (OCT), and fluorescein angiography (FA) at the baseline, 1-, 3-, 6-, 12-, and 24-month visits. MAIN OUTCOME MEASURES Changes in BCVA and OCT results. RESULTS The mean age of the patients was 59.4+/-11.1 years. The mean number of IVB injections per eye was 5.8 (range, 1-15 injections). In the 1.25-mg group at 1 month, BCVA improved from 20/150 (0.88 logarithm of the minimum angle of resolution [logMAR] units) to 20/107, 0.76 logMAR units (P<0.0001). The mean BCVA at 24 months was 20/75 (0.57 logMAR units; P<0.0001). Similar BCVA changes were observed in the 2.5-mg group: at 1 month, BCVA improved from 20/168 (0.92 logMAR units) to 20/118 (0.78 logMAR units; P = 0.02). The mean BCVA at 24 months was 20/114 (0.76 logMAR units; P<0.0001). In the 1.25-mg group, the mean central macular thickness (CMT) decreased from 466.5+/-145.2 microm at baseline to 332.2+/-129.6 microm at 1 month and 286.6+/-81.5 microm at 24 months (P<0.0001). Similar results were obtained in the 2.5-mg group. CONCLUSIONS Primary IVB at doses of 1.25 to 2.5 mg seem to provide stability or improvement in BCVA, OCT, and FA in DDME at 24 months. The results show no evident difference between IVB at doses of 1.25 or 2.5 mg.

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.

Endophthalmitis after pars plana vitrectomy: results of the Pan American Collaborative Retina Study Group.

Purpose: To determine the incidence of endophthalmitis after 20-, 23-, and 25-gauge pars plana vitrectomies (PPVs). Methods: Retrospective comparative case series of consecutive patients who underwent 20-, 23-, or 25-gauge PPV at 11 centers from Latin America between 2005 to 2009. Pars plana vitrectomy cases were identified through a search of the billing records of each institution. Cases of PPV performed in the management of trauma, endophthalmitis, and combined PPV phacoemulsification cases were excluded. Endophthalmitis was diagnosed by clinical criteria regardless of the microbiologic results. The incidence of post-PPV endophthalmitis was compared between 20-, 23-, and 25-gauge PPVs. Results: A total of 35,427 cases of PPV were identified during the study period (n = 19,865 for 20 gauge, n = 10,845 for 23 gauge, and n = 4,717 for 25 gauge). The 5-year post-PPV endophthalmitis incidence rates were 0.020% (4 of 19,865), 0.028% (3 of 10,845), and 0.021% (1 of 4,717) for 20 gauge, 23 gauge, and 25 gauge, respectively (P = 0.9685). Conclusion: Small-gauge transconjunctival PPV does not appear to increase the rates of post-PPV endophthalmitis.

Radial optic neurotomy for central retinal vein occlusion: Results of the pan-american collaborative retina study group (pacores)

Objective: To evaluate the complications after radial optic neurotomy (RON) for central retinal vein occlusion (CRVO). Methods: Seventy-three consecutive patients (73 eyes) with CRVO who were treated with RON participated in a retrospective, uncontrolled, interventional, multicenter case series at 7 institutions from 6 countries. Results: In the ischemic CRVO group (n = 53), 32% of eyes had an improvement in best-corrected visual acuity (BCVA) (mean, 5.5 lines), 35.8% had worse BCVA (mean, 6.4 lines), and 32% had BCVA that remained the same after RON. In the nonischemic CRVO group (n = 20), 50% of eyes had an improvement in BCVA (mean, 6.5 lines), 15% had worse BCVA (mean, 4.3 lines), and 35% had BCVA that remained the same after RON. Complications occurred in 71.2% of cases, including cataract in 17 eyes (23.2%), vitreous hemorrhage in 16 eyes (20.5%), persistent macular edema in 15 eyes (20.5%), neovascular glaucoma in 7 eyes (9.5%), anterior segment neovascularization in 5 eyes (6.8%), retinal detachment in 3 eyes (4.1%), and phthisis bulbi, choroidovitreal neovascularization, central retinal artery perforation, and optic nerve atrophy in 1 eye (1.3%) each. Conclusions: RON may improve visual acuity in some eyes with CRVO, but complications are common. In our series, surgery by itself did not seem to improve the outcome of CRVO when compared with its natural history.

Intravitreal bevacizumab for subfoveal choroidal neovascularization in age-related macular degeneration at twenty-four months: the Pan-American Collaborative Retina Study

PURPOSE To report the 24-month anatomic and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) response after primary intravitreal bevacizumab (IVB) (Avastin; Genentech Inc., San Francisco, CA) (1.25 or 2.5 mg) in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). DESIGN Retrospective, multicenter, interventional, comparative case series. PARTICIPANTS We reviewed the clinical records of 180 consecutive patients (207 eyes) with subfoveal CNV secondary to AMD at 9 centers from 8 countries. METHODS Patients were treated with at least 1 injection of IVB 1.25 mg (124 eyes [59.9%]) or 2.5 mg (83 eyes [40.1%]). Patients underwent ETDRS BCVA testing, ophthalmoscopic examination, optical coherence tomography (OCT), and fluorescein angiography (FA) at baseline and 1-, 3-, 6-, 12-, and 24-month visits. MAIN OUTCOME MEASURES Changes in BCVA and OCT. RESULTS The mean age of our patients was 74.3±7.5 years. The mean number of IVB injections per eye was 5.1 (range, 1-24 injections). In the 1.25 mg group, baseline BCVA improved from 20/235 (logarithm of the minimum angle of resolution [logMAR] 1.07) to 20/172 (logMAR 0.92) at 24 months (P<0.0001). Similar BCVA changes were observed in the 2.5 mg group. At baseline, the mean central macular thickness (CMT) by OCT in the 1.25 mg group was 308.4±127.52 μm, which was reduced to 269.35±97.92 μm, 262.1±94.81 μm, 264.03±97.06 μm, 245.91±89.52 μm, and 249.27±89.14 μm at 1, 3, 6, 12, and 24 months, respectively (P<0.0001). Similar changes were observed in the 2.5 mg group. In the 2.5 mg group, systemic complications included 2 new cases (2.6%) of arterial hypertension, 1 case (1.3%) of stroke, and 1 case (1.3%) of death. CONCLUSIONS Primary IVB at a dose of 1.25 or 2.5 mg seems to provide stability or improvement in BCVA, OCT, and FA in subfoveal CNV secondary to AMD at 24 months. Our results show no significant difference regarding BCVA with IVB at doses of 1.25 or 2.5 mg.

Phase I Clinical Evaluation of a Synthetic Oligosaccharide-Protein Conjugate Vaccine against Haemophilus influenzae Type b in Human Adult Volunteers

ABSTRACT Since 1989, we have been involved in the development of a vaccine against Haemophilus influenzae type b. The new vaccine is based on the conjugation of synthetic oligosaccharides to tetanus toxoid. Our main goals have been (i) to verify the feasibility of using the synthetic antigen and (ii) to search for new production alternatives for this important infant vaccine. Overall, eight trials have already been conducted with adults, children (4 to 5 years old), and infants. We have described herein the details from the first two phase I clinical trials conducted with human adult volunteers under double blind, randomized conditions. The participants each received a single intramuscular injection to evaluate safety and initial immunogenicity. We have found an excellent safety profile and an antibody response similar to the one observed for the control vaccine.

X-linked retinoschisis in three females from the same family: a phenotype-genotype correlation.

Purpose: To describe the clinical findings and outcome for three homozygous females affected with X-linked retinoschisis (XLRS) in a large Colombian family with 26 affected males. Methods: Retrospective review of charts for females from a family with XLRS who underwent complete ophthalmologic examinations, ancillary tests, clinical genetic evaluation, and molecular studies. Results: Three female patients (6 eyes) with clinical findings of XLRS were identified. The patients’ ages ranged from 10 to 37 years. Initial visual acuity was equal to or worse than 20/50 in 4 eyes (66%) of 2 patients. Four eyes (66%) were hyperopic. Intraocular pressure was normal in all eyes. Three eyes (50%) had cataracts, and vitreous veils were present in 3 (50%). The optic disk was pale in 6 eyes (100%). Foveal schisis was present in 6 eyes (100%). Peripheral retinal schisis was present in five eyes. A silvery gloss or tapetal-like retinal reflex or sheen was observed in 6 eyes (100%), and dendritic lines were found in 2 (33%). One eye had a retinal break, and one had a retinal detachment. Two eyes underwent cataract extraction; one patient underwent bilateral cryotherapy, one, laser treatment, and one, scleral buckling. Final visual acuity was 20/50 to 20/100 in 2 eyes and 20/200 to 20/400 in 4. Follow-up ranged from 7 to 22 years. Molecular analysis showed that all three female patients were homozygous for the allele 639delG of (on) the XRLS1 gene. Conclusions: Compared with their affected male relatives, three females from a family with XLRS had similar ocular findings and a more severe course of disease. These findings are explained by the fact that these patients were homozygous for a mutation in the XLRS1 gene.

Long-term effect of intravitreal triamcinolone in the nonproliferative stage of type II idiopathic parafoveal telangiectasia.

Purpose: To report the visual outcomes and ocular complications of intravitreal triamcinolone acetonide (IVTA) in the treatment of the nonproliferative stage of type II idiopathic parafoveal telangiectasia (IPT). Methods: Retrospective, multicenter, uncontrolled interventional case series of 19 eyes of 14 consecutive patients with the nonproliferative stage of IPT that had undergone at least one intravitreal injection of 4 mg of triamcinolone acetonide. Demographic, medical, and ocular data were obtained through chart review. The main outcome measures included best-corrected visual acuity at several timepoints of follow up and ocular complications. Results: At baseline the mean logMAR visual acuity was 0.83 ± 0.41 (Snellen 20/135, range 0.3–2). After an average follow-up of 21.2 months (range 6–44 months), the mean logMAR visual acuity remained essentially unchanged from baseline. At 3 months, the logMAR visual acuity was 0.86 ± 0.44 (Snellen 20/145, P = 0.8378), at 6 months 0.86 ± 0.42 (Snellen 20/145, P = 0.8149), at 12 months 0.87 ± 0.46 (Snellen 20/148, P > 0.9999), at 18 months 0.84 ± 0.35 (Snellen 20/138, P = 0.8385), and at the last follow-up 0.82 ± 0.44 (Snellen 20/132, P = 0.9301). Seven eyes were reinjected once. Ten of 19 eyes (53%) developed cataract (3 eyes underwent phacoemulsification and intraocular lens implantation) and 7 of 19 eyes (37%) had an elevated intraocular pressure, none of which required surgical treatment. Conclusion: IVTA does not seem to improve visual acuity in most eyes with the nonproliferative stage of IPT.

Intraocular pressure elevation after uncomplicated pars plana vitrectomy: results of the Pan American Collaborative Retina Study Group.

Purpose: To compare the incident rates of sustained elevation of intraocular pressure (IOP) after uncomplicated pars plana vitrectomy for idiopathic epiretinal membrane and the unoperated fellow eye. Methods: Retrospective multicenter study of 198 patients who underwent pars plana vitrectomy for an idiopathic epiretinal membrane that was followed for at least 12 months. The diagnosis of sustained IOP elevation was defined as an elevation of IOP ≥24 mmHg or an increase of ≥5 mmHg in the IOP from baseline on 2 separate visits that warranted the initiation of ocular hypotensive therapy. The main outcome measured was the development of sustained IOP elevation as defined above. Results: Patients were followed for an average of 47.3 ± 24 months (range, 12–106 months). In the vitrectomized eyes, 38 of the 198 (19.2%) patients developed elevated IOP compared with 9 of the 198 (4.5%) unoperated fellow eyes (P < 0.0001, Fisher exact test; odds ratio, 4.988). Possible risk factors include a family history of open-angle glaucoma (P = 0.0004 Fisher exact test; odds ratio, 7.206) and cataract surgery (P = 0.0270 Fisher exact test; odds ratio, 2.506). Conclusion: Uncomplicated PPV seems to increase the IOP, particularly in those who are pseudophakic and have a family history of open-angle glaucoma. This increase in IOP may lead to glaucomatous damage if not managed appropriately. Patients with a previous PPV need to be followed by an ophthalmologist to monitor the IOP in the vitrectomized eye.

Vitreoretinal surgery for macular hole after laser assisted in situ keratomileusis for the correction of myopia

Ams: To describe the characteristics and surgical outcomes of full thickness macular hole surgery after laser assisted in situ keratomileusis (LASIK) for the correction of myopia. Methods: 13 patients (14 eyes) who developed a macular hole after bilateral LASIK for the correction of myopia participated in the study. Results: Macular hole formed 1–83 months after LASIK (mean 13 months). 11 out of 13 (84.6%) patients were female. Mean age was 45.5 years old (25–65). All eyes were myopic (range −0.50 to −19.75 dioptres (D); mean −8.4 D). Posterior vitreous detachment (PVD) was not present before and was documented after LASIK on 42.8% of eyes. Most macular hole were unilateral, stage 4 macular hole, had no yellow deposits on the retinal pigment epithelium, had no associated epiretinal membrane, were centric, and had subretinal fluid. The mean diameter of the hole was 385.3 μm (range 200–750 μm). A vitrectomy closed the macular hole on all eyes with an improvement on final best corrected visual acuity (VA) on 13 out of 14 (92.8%) patients. Conclusions: This study shows that vitreoretinal surgery can be successful in restoring vision for most myopic eyes with a macular hole after LASIK.