Age-related macular degeneration (AMD) has become a major public health problem and a leading cause of blindness in industrialized nations. AMD results from the ageing eye’s inability to metabolize and dispose completely of photoreceptor outer segments and other waste products. As a result, lipids, particularly apolipoproteins, accumulate within Bruch’s membrane, leading to chronic ischemia and inflammation. The subsequent upregulation of inflammatory cytokines and growth factors, including vascular endothelial growth factor (VEGF), induces the growth of neovascular membranes from the choriocapillaris into the subretinal or subretinal pigment epithelium spaces. To counter this, intravitreally administered drugs (pegaptanib, bevacizumab, ranibizumab) that specifically target VEGF have become the standard treatment for exudative AMD. Aflibercept, a recently approved fusion protein, binds to all isoforms of both VEGF-A and placental growth factor with high affinity. Phase III trials showed that monthly or every other month injections of aflibercept prevent vision loss (fewer than 15 letters) in 95% of patients. Additionally, aflibercept injections every 4 or 8 weeks produce average vision gains of 6.9 letters to 10.9 letters, comparable with those achieved with monthly ranibizumab. After one year of regularly administered aflibercept injections, patients required an average of only 4.2 injections during the second year. Aflibercept promises to decrease the injection frequency required for many patients and appears to serve as an effective “salvage” therapy for patients who respond poorly to other anti-VEGF drugs.

Vascular endothelial growth factor (VEGF) plays an important role in both physiologic and pathologic angiogenesis and contributes to increased permeability across both the blood-retinal and blood-brain barriers. After 2 decades of extensive research into the VEGF families and receptors, specific molecules have been targeted for drug development, and several medications have received US Food and Drug Administration approval. Bevacizumab, a full-length antibody against VEGF approved for the intravenous treatment of advanced carcinomas, has been used extensively in ophthalmology for exudative age-related macular degeneration, diabetic retinopathy, retinal vein occlusions, retinopathy of prematurity, and other chorioretinal vascular disorders. Pegaptanib and ranibizumab have been developed specifically for intraocular use, whereas the soon-to-be-introduced aflibercept (VEGF Trap-Eye) is moving through clinical trials for both intraocular and systemic use. Although these drugs exhibit excellent safety profiles, ocular and systemic complications, particularly thromboembolic events, remain a concern in patients receiving therapy. Patients experiencing adverse events that may be related to VEGF suppression should be carefully evaluated by both the ophthalmologist and the medical physician to reassess the need for intraocular therapy and explore the feasibility of changing medications. For this review a search of PubMed from January 1, 1985 through April 15, 2011, was performed using the following terms (or combination of terms): vascular endothelial growth factors, VEGF, age-related macular degeneration, diabetic retinopathy, retina vein occlusions, retinopathy of prematurity, intravitreal injections, bevacizumab, ranibizumab, and VEGF Trap. Studies were limited to those published in English. Other articles were identified from bibliographies of retrieved articles and archives of the author.

Background

This analysis compared outcomes for same-day (under a no-move, no-wait policy) versus delayed vitrectomy for intravitreal crystalline retained lens fragments after surgery for age-related cataract.

Methods

This was a retrospective, nonrandomized treatment comparison cohort study with a consecutive series of 35 eyes (23 same-day, 12 delayed) receiving both cataract surgery and vitrectomy at the Mayo Clinic Florida between 1999 and 2010. Outcome measures included visual acuity (VA), glaucoma progression, visual utility, and complications. Several techniques (bootstrapping, robust confidence intervals, jackknifing, and a homogeneous sample) were used to reduce selection bias and increase confidence in our small sample’s results.

Results

No significant baseline treatment group differences. Mean previtrectomy delay (12 eyes) was 40.9 days (median 29.5, range 1–166). Mean postvitrectomy follow-up (35 eyes) was 47.5 months (median 40.5, range 3.1–123.5). Same-day patients had significantly better final VA (adjusted for age [t = −2.14, P = 0.040] and precataract surgery VA [t = −2.98, P = 0.006]); a higher rate of good final VA (≥20/40), 78.3% (18/23) versus 58.3% (7/12); a lower rate of bad final VA (≤20/200), 4.3% (1/23) versus 25.0% (3/12); and fewer final retinal conditions, 4.3% (1/23) versus 50.0% (6/12). Same-day patients also had marginally significant better mean final VA in the operated eye (20/40 versus 20/90, Z = 1.51, P = 0.130) despite poorer initial VA (20/98 versus 20/75) and higher age (3+ years), better final visual utility, and longer survival times for better VA. Among patients with preexisting glaucoma, same-day patients experienced significantly less differential (operated versus nonoperated eye) glaucoma progression.

Conclusion

Results favored same-day patients, who experienced better final VA and visual utility, less differential glaucoma progression, and fewer complications. Results need confirmation with larger samples.

Cytomegalovirus (CMV) retinitis is the most common cause of vision loss in patients with acquired immunodeficiency syndrome (AIDS). CMV retinitis afflicted 25% to 42% of AIDS patients in the pre-highly active antiretroviral therapy (HAART) era, with most vision loss due to macula-involving retinitis or retinal detachment. The introduction of HAART significantly decreased the incidence and severity of CMV retinitis. Optimal treatment of CMV retinitis requires a thorough evaluation of the patient’s immune status and an accurate classification of the retinal lesions. When retinitis is diagnosed, HAART therapy should be started or improved, and anti-CMV therapy with oral valganciclovir, intravenous ganciclovir, foscarnet, or cidofovir should be administered. Selected patients, especially those with zone 1 retinitis, may receive intravitreal drug injections or surgical implantation of a sustained-release ganciclovir reservoir. Effective anti-CMV therapy coupled with HAART significantly decreases the incidence of vision loss and improves patient survival. Immune recovery uveitis and retinal detachments are important causes of moderate to severe loss of vision. Compared with the early years of the AIDS epidemic, the treatment emphasis in the post- HAART era has changed from short-term control of retinitis to long-term preservation of vision. Developing countries face shortages of health care professionals and inadequate supplies of anti-CMV and anti-HIV medications. Intravitreal ganciclovir injections may be the most cost effective strategy to treat CMV retinitis in these areas.