Franco M. Recchia

Anti–Vascular Endothelial Growth Factor Pharmacotherapy for Age-Related Macular Degeneration: A Report by the American Academy of Ophthalmology

OBJECTIVE To examine the evidence about the safety and efficacy of anti-vascular endothelial growth factor (VEGF) pharmacotherapies for the treatment of neovascular age-related macular degeneration (AMD). DESIGN Literature searches were conducted in May and October 2007 in PubMed with no date restrictions, limited to articles published in English, and in the Cochrane Central Register of Controlled Trials without a language limitation and yielded 310 citations. The first author reviewed the abstracts of these articles and selected 73 articles of possible clinical relevance for review by the panel. The panel deemed 64 of these articles sufficiently clinically relevant to review in full text and assigned ratings of level of evidence to each of the selected articles with the guidance of the panel methodologists. RESULTS Eleven studies provided level I evidence for intravitreal pegaptanib and ranibizumab for neovascular AMD; there were no studies rated level I for bevacizumab for neovascular AMD. Five studies were rated as level II, which included studies of ranibizumab and bevacizumab, and the remaining 38 articles retrieved were rated as level III. The studies do not provide information about long-term results or the value (comparative effectiveness) and cost-effectiveness of combined therapies. CONCLUSIONS Review of the available literature to date suggests that anti-VEGF pharmacotherapy, delivered by intravitreal injection, is a safe and effective treatment for neovascular AMD for up to 2 years. There is level I evidence to support this conclusion for pegaptanib and ranibizumab, but none for bevacizumab at this time.

Small-gauge pars plana vitrectomy: a report by the American Academy of Ophthalmology.

OBJECTIVE To review available peer-reviewed publications to evaluate the safety profile and visual outcomes associated with small-gauge pars plana vitrectomy. METHODS Literature searches of the PubMed and the Cochrane Library databases were last conducted on August 5, 2009, with no date restrictions. The searches were limited to articles published in English. These searches retrieved 328 articles, of which 76 were deemed topically relevant and rated according to strength of evidence. RESULTS On the basis of level II and level III evidence, the overall safety profile of small-gauge pars plana vitrectomy is similar to that established for conventional 20-gauge pars plana vitrectomy and provides comparable visual acuity results. An increased incidence of infectious endophthalmitis after 25-gauge vitrectomy was reported in 2 comparative studies, but this was not found in multiple, larger, more recent studies, perhaps due to modifications in case selection and surgical technique over time. Compared with 20-gauge vitrectomy, small-gauge vitrectomy is associated with significantly lower levels of patient discomfort and ocular inflammation, and the time required for improvement in visual acuity is shorter. CONCLUSIONS The technological advances of small-gauge vitrectomy seem to afford visual benefit comparable with that seen with traditional 20-gauge surgery, with more rapid healing, less discomfort, and an acceptably low incidence of adverse events comparable with those observed with conventional 20-gauge vitrectomy. As surgical techniques evolve and clinical experience grows, continued close surveillance is necessary for an accurate assessment of complications.

Systemic disorders associated with retinal vascular occlusion.

Occlusions of the retinal arterial and venous circulations are common causes of severe visual decline and can affect all age groups. Acute retinal arterial obstruction is often associated with critical cerebrovascular and cardiovascular disease that may require systemic treatment. Retinal venous obstruction may be the presentation of significant systemic hypertension, diabetes mellitus, and a greater risk for cardiovascular morbidity. Additional metabolic and hematologic abnormalities have been identified in patients with retinal occlusive disease. The authors review recent advances in the study of systemic conditions associated with retinal vascular occlusions and offer guidelines for appropriate medical evaluation of patients with retinal occlusive disease.

Intravitreal bevacizumab as adjunctive treatment for retinopathy of prematurity

BACKGROUND While laser photocoagulation remains the standard of care in the treatment of advanced retinopathy of prematurity (ROP), regression is not seen in all cases (especially in aggressive posterior disease) following laser alone. We report the results of the use of the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in eyes with ROP at high risk for progression. METHODS Records of all infants with ROP treated with bevacizumab were reviewed. Bevacizumab was given when conventional laser therapy was not possible in patients with poor pupillary dilation from iris rubeosis, dense vitreous hemorrhage, or increasing vascular activity and vitreoretinal traction despite completed laser therapy. We recorded birth weight, gestational age at birth, severity of ROP, anatomic result, any additional ophthalmic interventions, and early or late adverse systemic effects. RESULTS Thirteen eyes of 7 infants (median gestational age, 25 weeks; median birth weight, 700 g; follow-up, 9 months [range, 2-17]) were treated with an intravitreal injection of 0.75 mg bevacizumab under sterile conditions by 1 surgeon following detailed discussion with family and attending neonatologists. Injection was not used as monotherapy in any case. Definitive treatment (laser or vitrectomy) was completed successfully within 72 hours of injection. No systemic complication attributable to bevacizumab treatment has been recorded within 2 to 17 months of follow-up. CONCLUSIONS Treatment with bevacizumab may be used to improve visualization for more definitive laser or surgical treatment and may facilitate disease regression without obvious systemic toxicity. Optimization of dosing, timing, and indications will require additional study.

Anti–Vascular Endothelial Growth Factor Pharmacotherapy for Diabetic Macular Edema: A Report by the American Academy of Ophthalmology

OBJECTIVE To review the evidence regarding the safety and efficacy of current anti-vascular endothelial growth factor (VEGF) pharmacotherapies for the treatment of diabetic macular edema (DME). METHODS Literature searches last were conducted in September 2011, in PubMed with no date restrictions, limited to articles published in English, and in the Cochrane Library without a language limitation. The combined searches yielded 532 citations, of which 45 were deemed clinically relevant for the authors to review in full text and to assign ratings of level of evidence to each of the selected studies with the guidance of the panel methodologists. RESULTS At this time, there are 5 studies that provide level I evidence for intravitreal ranibizumab, alone or in combination with other treatments for DME. There is also 1 study that provides level I evidence for intravitreal pegaptanib sodium for DME. Nine studies reviewed were rated as level II, and 2 additional studies reviewed were graded as level III. Most studies do not provide information about long-term results (i.e., more than 2 years of follow-up) or the comparative efficacy of anti-VEGF pharmacotherapies. CONCLUSIONS Review of the available literature indicates that anti-VEGF pharmacotherapy, delivered by intravitreal injection, is a safe and effective treatment over 2 years for DME. Further evidence is required to support the long-term safety of these pharmacotherapies and their comparative efficacy.

Antibiotic resistance of conjunctiva and nasopharynx evaluation study: a prospective study of patients undergoing intravitreal injections.

PURPOSE To determine the baseline antibiotic susceptibility patterns of conjunctival and nasopharyngeal flora isolated from patients undergoing intravitreal (IVT) injections for choroidal neovascularization (CNV). DESIGN Prospective, observational study. PARTICIPANTS Forty-eight eyes of 24 patients undergoing unilateral IVT injections for CNV. METHODS Bilateral conjunctival and unilateral nasopharyngeal cultures on the treatment side were taken before application of any topical medications. MAIN OUTCOME MEASURES Bacterial isolates were identified and tested for antibiotic susceptibility to 16 different antibiotics using the Kirby-Bauer disc diffusion technique. RESULTS A total of 57 bacterial isolates were obtained from the conjunctiva of 48 eyes. Coagulase-negative staphylococci (CNS) accounted for 37 of the 57 isolates (65%). The most common CNS organisms were Staphylococcus epidermidis and Staphylococcus lugdunensis accounting for 73% and 11% of CNS isolates, respectively. More than half of S. epidermidis isolates demonstrated some level of resistance to ofloxacin and levofloxacin, and 33% and 37% of isolates showed some level of resistance against gatifloxacin and moxifloxacin, respectively. Some 60% and 30% of CNS isolates were resistant to ≥ 3 and ≥ 5 antibiotics, respectively. Among the 24 nasopharyngeal cultures, 8 (33%) grew Staphylococcus aureus, and 1 of the 8 isolates (13%) was resistant to all penicillin, cephalosporin, macrolide, and fluoroquinolone antibiotics tested. CONCLUSIONS Our results demonstrate subtantial levels of resistance to third- and fourth-generation fluoroquinolones and multiresistance among ocular CNS isolated from patients undergoing IVT injections for CNV.

Foveal dysplasia evident by optical coherence tomography in patients with a history of retinopathy of prematurity.

Purpose: To describe the optical coherence tomography (OCT) findings for patients with a history of retinopathy of prematurity (ROP). Methods: Clinical records, fundus photographs, and OCT findings for consecutive patients aged 8 years and older who had a history of ROP were reviewed. The main outcome measures were best-corrected visual acuity, central foveal thickness (CFT), macular anatomy, and foveal contour by OCT. Results: Twenty eyes of 12 patients (median age, 15 years) were studied. Median gestational age at birth was 25 weeks. Six eyes had received peripheral retinal ablation for threshold ROP. Median best-corrected visual acuity was 20/40 (range, 20/20 to counting fingers). CFT was >220 μm in 70% of eyes and >240 μm in 35% of eyes. In all eyes, foveal contour was abnormal, with foveal depression either absent (n = 7 [35%]) or shallow (n = 13 [65%]). Preservation of multiple inner retinal layers within the fovea was seen in 14 eyes (70%). Vitreomacular traction or subretinal fluid was not seen in any eye. Conclusions: Anomalies in foveal anatomy by OCT may be a vestige of prematurity, appear to be independent of prior retinopexy, and can still be associated with excellent visual acuity.

Treatment of cystoid macular edema with the new-generation NSAID nepafenac 0.1%.

Purpose: To describe the use of nepafenac 0.1% for cystoid macular edema (CME). Methods: This was a multicenter retrospective review of 22 CME cases (20 patients) treated with nepafenac 0.1% (six with concomitant prednisolone acetate 1%) from December 2005 to April 2008: three acute pseudophakic CME cases, 13 chronic/recalcitrant pseudophakic CME cases, and six cases of uveitic CME. Pre- and post-treatment retinal thickness and visual acuity were reported. Results: Following treatment for six weeks to six months, six eyes with uveitic CME showed a mean retinal thickness improvement of 227 ± 168.1 μm; mean best-corrected visual acuity (BCVA) improvement was 0.36 ± 0.20 logMAR. All three cases of acute pseudophakic CME improved after four to 10 weeks of nepafenac, with a mean improvement in retinal thickness of 134 ± 111.0 μm. BCVA improved in two patients (0.16 and 0.22 logMAR) but not in the third due to underlying retinal pigment epithelium changes. Thirteen eyes with chronic/recalcitrant pseudophakic CME demonstrated a mean improvement in retinal thickness of 178 ± 128.7 μm after nepafenac and mean BCVA improvement of 0.33 ± 0.19 logMAR. Conclusion: The positive outcomes of these 22 eyes strongly suggest that nepafenac 0.1% is a promising drug for the treatment of CME. Additional study under randomized controlled conditions is warranted.

Long-term trends in intraocular pressure after pars plana vitrectomy.

Purpose: To evaluate the effect of vitrectomy on intraocular pressure (IOP). Methods: Retrospective cohort study. Medical records of 101 eyes of 101 patients undergoing nonemergent vitrectomy were reviewed for rates of open-angle glaucoma, increased IOP of >4 mmHg from baseline, change in IOP from baseline, and cataract formation. Preoperative and last measured IOPs were recorded. Baseline risk characteristics including lens status and diabetes were analyzed. Main outcome measures were 1) incidence of open-angle glaucoma; 2) increase in IOP of >4 mmHg; and 3) change in IOP. Results: Mean follow-up was 49 months (range, 12-105 months). Mean baseline IOP was 15.3 mmHg, and mean final IOP was 15.8 mmHg (P = 0.3). At the most recent examination, 35 study eyes had a decrease in IOP from baseline, while 14 eyes had no change and 52 eyes had an increase in IOP. Four study eyes were newly diagnosed with ocular hypertension. No study eye developed open-angle glaucoma or required medical, laser, or surgical treatment for glaucoma. Incidence of increased IOP of >4 was 7% at 4 years and 34% at 8 years. Subgroup analysis of 66 patients comparing study eyes with nonvitrectomized fellow eyes demonstrated no significant difference in rates of increased IOP of >4 (P = 0.85). Neither diabetes nor pseudophakia was associated with significantly increased IOP. Conclusion: In this series, vitrectomy does not appear to increase IOP even after removal of the crystalline lens.

Detection of Clinically Significant Retinopathy of Prematurity Using Wide-angle Digital Retinal Photography: A Report by the American Academy of Ophthalmology

OBJECTIVE To evaluate the accuracy of detecting clinically significant retinopathy of prematurity (ROP) using wide-angle digital retinal photography. METHODS Literature searches of PubMed and the Cochrane Library databases were conducted last on December 7, 2010, and yielded 414 unique citations. The authors assessed these 414 citations and marked 82 that potentially met the inclusion criteria. These 82 studies were reviewed in full text; 28 studies met inclusion criteria. The authors extracted from these studies information about study design, interventions, outcomes, and study quality. After data abstraction, 18 were excluded for study deficiencies or because they were superseded by a more recent publication. The methodologist reviewed the remaining 10 studies and assigned ratings of evidence quality; 7 studies were rated level I evidence and 3 studies were rated level III evidence. RESULTS There is level I evidence from ≥5 studies demonstrating that digital retinal photography has high accuracy for detection of clinically significant ROP. Level III studies have reported high accuracy, without any detectable complications, from real-world operational programs intended to detect clinically significant ROP through remote site interpretation of wide-angle retinal photographs. CONCLUSIONS Wide-angle digital retinal photography has the potential to complement standard ROP care. It may provide advantages through objective documentation of clinical examination findings, improved recognition of disease progression by comparing previous photographs, and the creation of image libraries for education and research. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.