Does Dry Eye Disease Severity Impact Efficacy of Varenicline Solution Nasal Spray on Sign and Symptom Treatment Outcomes?

SIGNIFICANCE: There is a clinical necessity for dry eye disease treatments that perform across a broad range of presenting patient severities. Varenicline solution nasal spray (VNS), a unique cholinergic agonist ocular surface-sparing nasal spray therapy, demonstrated significant improvement in both signs and symptoms of dry eye disease in subjects with mild, moderate, and severe symptoms as the clinical studies enrolled a more real-world patient population. PURPOSE: This study evaluated efficacy outcomes for VNS in patients with mild-moderate and severe dry eye disease. METHODS: An analysis of integrated data from two randomized clinical trials, ONSET-1 (NCT03636061) and ONSET-2 (NCT04036292) (vehicle control [VC], n = 294; VNS 0.03 mg, n = 308), was performed. Adults 22 years or older with dry eye disease, Ocular Surface Disease Index score of ≥23, corneal fluorescein staining score of ≥2 in ≥1 regions/≥4 all regions, and Schirmer Test Score (STS) of ≤10 mm (no restrictions on Eye Dryness Score [EDS]) were included in this study. Efficacy was evaluated using analysis of covariance among pre-specified subgroups of mild-moderate and severe baseline disease severity defined by STS (≤5 vs. >5) and EDS (<60 vs. ≥60). Consistency of effect was evaluated by interaction tests. RESULTS: No treatment-subgroup interactions were observed for all end points ( P > .05). The odds of achieving a ≥10-mm improvement in STS for VNS versus VC for patients with baseline STS ≤5 and >5 were 3.4(95% confidence interval, 2.0 to 5.6) and 2.3(1.3 to 4.0) and for EDS of <60 and ≥60 were 3.4(1.9 to 6.1) and 2.5(1.5 to 4.0). Least-squares mean treatment/VC differences in change from baseline in EDS for patients with baseline STS ≤5 or >5 were -7.4(95% confidence interval, -12.5 to -2.4) and -2.8(-8.7 to 3.1); EDS of <60 and ≥60 were -2.9(-8.3 to 2.5) and -8.1(-13.6 to -2.6). CONCLUSIONS: Compared with VC, VNS improved tear production and patient-reported symptoms in patients with dry eye disease, demonstrating consistency of effect regardless of initial presenting severity.

A Prospective, Randomized Trial of Povidone-Iodine 0.6% and Dexamethasone 0.1% Ophthalmic Suspension for Acute Bacterial Conjunctivitis.

PURPOSE: To evaluate the efficacy and safety of a topical ophthalmic suspension combination of povidone-iodine 0.6% (PVP-I) and dexamethasone 0.1% (DEX) for infectious and inflammatory components of bacterial conjunctivitis. DESIGN: Randomized, double-masked, multicenter, phase 3 clinical trial. METHODS: Subjects of all ages (those <3 months had to be full-term) with a diagnosis of bacterial conjunctivitis were randomized 3:1:3 to either PVP-I/DEX, PVP-I alone, or placebo. The primary endpoint was clinical resolution in the study eye, and the key secondary efficacy endpoint was bacterial eradication, both at the day 5 visit. Adverse events (AEs) were documented at all visits. RESULTS: Overall, 753 subjects were randomized (intent-to-treat [ITT] population; PVP-I/DEX [n = 324]; PVP-I [n = 108]; placebo [n = 321]); mean and standard deviation (SD) age was 44.3 (22.9) years, and most were female (61.2%) and white (78.1%). In all treatment groups, mean treatment compliance was >98%. The modified ITT population for the efficacy analysis comprised 526 subjects. In the study eye at the day 5 visit, clinical resolution was achieved by 50.5% (111/220) subjects in the PVP-I/DEX group vs 42.8% (95/222) in the placebo group (P = .127), and bacterial eradication was achieved by 43.3% (94/217) and 46.8% (102/218), respectively (P = .500). Treatment-emergent AEs were experienced by 32.8% (106/323), 39.8% (43/108), and 19.0% (61/321) of subjects in the safety population treated with PVP-I/DEX, PVP-I, and placebo, respectively (most mild in severity). CONCLUSION: In this study, PVP-I/DEX did not demonstrate additional benefit in clinical efficacy compared with placebo in subjects with bacterial conjunctivitis.

Long-term Safety and Ocular Hypotensive Efficacy Evaluation of Netarsudil Ophthalmic Solution: Rho Kinase Elevated IOP Treatment Trial (ROCKET-2).

PURPOSE: To evaluate netarsudil 0.02% ophthalmic solution in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). DESIGN: Double-masked, randomized, multicenter, parallel-group, noninferiority clinical study. METHODS: After a washout of all prestudy ocular hypotensive medications, 756 eligible patients with elevated IOP were randomized to receive netarsudil 0.02% once a day (q.d.) (251); netarsudil 0.02% twice a day (b.i.d.) (254); or timolol 0.5% b.i.d. (251) for 12 months, as well as a noninterventional Corneal Observation Study (COS) for patients manifesting cornea verticillata. RESULTS: On treatment, mean IOP at 8:00 AM decreased from a baseline IOP of 22.5-22.6 mm Hg to 17.9-18.8 mm Hg, 17.2-18.0 mm Hg, and 17.5-17.9 mm Hg for netarsudil q.d., netarsudil b.i.d., and timolol, respectively, over 12 months. The most frequently reported adverse events (AEs) were ocular, with the most frequent ocular AE being conjunctival hyperemia, with an incidence of 61%, 66%, and 14%, respectively. The next most frequent AEs were corneal deposits (corneal verticillata), with an incidence of 26%, 25%, and 1%, respectively, and conjunctival hemorrhage (typically petechial), with an incidence of 20%, 19%, and 1%, respectively. All 3 AEs were generally scored as mild, with conjunctival hyperemia and/or hemorrhage appearing sporadically during the study. In the observational follow-up component of this study, there was no clinically meaningful impact of corneal verticillata on visual function in affected patients. CONCLUSIONS: In this randomized, double-masked trial, once-daily dosing of netarsudil 0.02% was effective, consistently lowering IOP through 12 months, and was tolerated by the majority of patients.

Donor, Recipient, and Operative Factors Associated With Increased Endothelial Cell Loss in the Cornea Preservation Time Study.

Importance: Determining factors associated with endothelial cell loss after Descemet stripping automated endothelial keratoplasty (DSAEK) could improve long-term graft survival. Objective: To evaluate the associations of donor, recipient, and operative factors with endothelial cell density (ECD) 3 years after DSAEK in the Cornea Preservation Time Study. Design, Setting, and Participants: This cohort study was a secondary analysis of data collected in a multicenter, double-masked, randomized clinical trial. Forty US clinical sites with 70 surgeons participated, with donor corneas provided by 23 US eye banks. Individuals undergoing DSAEK for Fuchs dystrophy or pseudophakic/aphakic corneal edema were included. Interventions: The DSAEK procedure, with random assignment of a donor cornea with a preservation time of 0 to 7 days or 8 to 14 days. Main Outcomes and Measures: Endothelial cell density at 3 years as determined by a reading center from eye bank and clinical specular or confocal central endothelial images. Results: The study included 1090 participants (median age, 70 years) with 1330 affected eyes (240 bilateral cases [22.0%]), who underwent DSAEK for Fuchs dystrophy (1255 eyes [94.4%]) or pseudophakic/aphakic corneal edema (PACE) (75 eyes [5.6%]). Of these, 801 eyes (60.2%) belonged to women and 1207 (90.8%) to white individuals. A total of 749 participants (913 eyes; 164 [21.9%] bilateral cases) had functioning grafts with acceptable endothelial images preoperatively and at 3 years postoperatively and were included in this analysis. Factors associated with a lower ECD at 3 years (estimated effect with 99% CI) in the final multivariable model included donors with diabetes (-103 [-196 to -9] cells/mm2), lower screening ECD (-234 [-331 to -137] per 500 cells/mm2), recipient diagnosis of PACE (-257 [-483 to -31] in cells/mm2), and operative complications (-324 [-516 to -133] in cells/mm2). Endothelial cell loss (ECL) from a preoperative measurement to a 3-year postoperative measurement was 47% (99% CI, 42%-52%) for participants receiving tissue from donors with diabetes vs 43% (99% CI, 39%-48%) without diabetes; it was 53% (99% CI, 44%-62%) for participants diagnosed with PACE vs 44% (99% CI, 39%-49%) for those diagnosed with Fuchs dystrophy, and 55% (99% CI, 48%-63%) in participants who experienced operative complications vs 44% (99% CI, 39%-48%) in those who did not. No other donor, recipient, or operative factors were significantly associated with 3-year ECD. Conclusions and Relevance: Donor diabetes, lower screening ECD, a PACE diagnosis in the recipient, and operative complications were associated with lower ECD at 3 years after DSAEK surgery and may be associated with long-term graft success. While causation cannot be inferred, further studies on the association of donor diabetes and PACE in recipients with lower 3-year ECD warrant further study.

Histopathologic Clues in Diagnosing Oral Mucosal Grafts to the Conjunctiva.

Excised redundant, forniceal "conjunctival" tissue from a 67-year-old man who experienced a chemical injury to his OS 25 years earlier was evaluated histopathologically with the hematoxylin-eosin, periodic acid Schiff (PAS) with and without diastase, mucicarmine, and Alcian blue methods. Additional immunoperoxidase testing for gross cystic disease fluid protein-15 (GCDFP-15) was undertaken. Non-keratinizing squamous epithelium composed of 8 to 10 layers of swollen keratinocytes without goblet cells surmounted a variably dense and well-vascularized collagenized lamina propria deep to which, in submucosal fibroadipose tissue, was embedded an accessory gland. The acini of the gland were composed of both GCDFP-15-positive serous cells and mucicarmine-positive goblet cells, indicating they were seromucinous rather than entirely serous, as is characteristic of normal lacrimal glandular tissue. Different features of the surface epithelium, the lamina propria, and the submucosa can separate the conjunctival and oral mucous membranes. A close analysis of the cytologic composition of associated accessory glands can reinforce the correct diagnosis of an oral mucous membrane graft when the past surgical history is unclear, because only serous cells but not mucocytes comprise the lacrimal glandular units.

Drug-induced corneal epithelial changes.

Drugs across many pharmacologic classes induce corneal epithelial changes. Many of these drugs have cationic amphiphilic structures, with a hydrophobic ring and hydrophilic cationic amine side chain that allow them to cross cell membranes. These drugs lead to intracellular phospholipid accumulation, often manifested in the cornea by vortex keratopathy, with no effect on visual acuity and few ocular symptoms. Other drugs, notably antineoplastic agents, produce a fine diffuse corneal haze, sometimes accompanied by decreased vision that can be dose limiting. Still other medications cause crystalline epithelial precipitation that might require debridement for resolution. An understanding of the variety of drugs involved, the multiple mechanisms responsible, and the systemic diseases that produce similar changes can lead to improved management strategies for patients with corneal epithelial deposits. In most cases, drug therapy need not be modified or discontinued, but if visual acuity is affected, close collaboration with the prescribing physician can result in determining an optimized dose that treats systemic disease and minimizes these deposits. Additionally, close monitoring might be required if the drug is also associated with other ocular findings, such as optic neuropathy or retinopathy.

Hydrogel sealant versus sutures to prevent fluid egress after cataract surgery.

PURPOSE: To evaluate the effectiveness of a hydrogel sealant versus a suture in preventing fluid egress after wound leakage in cataract surgery. SETTING: Twenty-four ophthalmic clinical practices in the United States. DESIGN: Prospective randomized parallel-arm controlled multicenter subject-masked study. METHODS: Healthy patients having uneventful clear corneal incision (CCI) cataract surgery were eligible for the study. Spontaneous and provoked fluid egress from wounds was evaluated at the time of surgery using a calibrated force gauge. Eyes with leakage were randomized to receive a hydrogel sealant (Resure) or a nylon suture at the main incision site. Incision leakage was reevaluated 1, 3, 7, and 28 days postoperatively. RESULTS: Of 500 eyes, 488 had leakage at the time of cataract surgery. The leak was spontaneous in 244 cases (48.8%), and 488 (97.6%) of all incisions leaked with 1.0 ounce or less of applied force. After randomization, 12 (4.1%) of 295 eyes in the sealant group and 60 (34.1%) of 176 eyes in the suture group had wound leakage with provocation (P<.0001). The overall incidence of adverse ocular events was statistically significantly lower in the sealant group than in the suture group (P<.05). CONCLUSIONS: In this study, 97.6% of CCIs leaked after cataract surgery. The hydrogel sealant was safe and effective and better than a suture for the intraoperative management of CCIs with leakage as seen on Seidel testing and for the prevention of postoperative fluid egress.

Randomized comparison of postoperative use of hydrogel ocular bandage and collagen corneal shield for wound protection and patient tolerability after cataract surgery.

PURPOSE: To compare the safety and efficacy of a hydrogel bandage and a collagen corneal shield in providing wound protection and relief of pain/discomfort in the acute period after uneventful unilateral clear corneal phacoemulsification cataract surgery with foldable intraocular lens (IOL) implantation. SETTING: Seventeen investigational sites in the United States. DESIGN: Prospective randomized single-masked parallel study. METHODS: The study comprised patients scheduled to have unilateral clear corneal cataract surgery with posterior chamber intraocular lens implantation. The patients were examined preoperatively and frequently for 30 days postoperatively. The design was a noninferiority study of the 2 primary endpoints, device performance and maximum reported postoperative pain. RESULTS: The device performance success was 78.6% (228/290) for the hydrogel bandage and 26.5% (26/98) for the corneal shield (P<.0001 for noninferiority). Analyses indicated that the hydrogel bandage was superior to the corneal shield in device performance (P<.001; difference = 52.1%; 95% confidence interval, 41.6%-61.4%). The maximum postoperative pain/discomfort score of the hydrogel bandage (mean 1.3 ± 1.8 [SD]; scale 0 to 10) was noninferior to that of the corneal shield (1.1 ± 1.6) in the first 4 hours after surgery (P<.001). Adverse events in the cataract surgeries were reported in 22.2% (70/316) and 36.5% (38/104) of hydrogel bandage patients and corneal shield patients, respectively (P = .0045). CONCLUSION: The hydrogel bandage was safe and effective for ocular surface protection and relief of pain/discomfort when applied topically to clear corneal incisions used in cataract or IOL implantation surgery. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosures are found in the footnotes.

Twice-daily, preservative-free ketorolac 0.45% for treatment of inflammation and pain after cataract surgery.

PURPOSE: To evaluate the efficacy and safety of twice-daily, preservative-free ketorolac 0.45% (Acuvail; Allergan, Inc, Irvine, California, USA) administration for treatment of inflammation and pain after cataract surgery. DESIGN: Prospective, randomized trial. METHODS: Two multicenter, double-masked studies randomized 511 cataract surgery patients (2:1) to receive twice-daily ketorolac 0.45% or vehicle in the operative eye for 16 days, beginning 1 day before surgery. The primary efficacy end point was the percentage of patients with a summed ocular inflammation score of 0 for anterior chamber cell and flare on postoperative day 14. The main secondary efficacy end point was the percentage of patients with no pain on postoperative day 1. RESULTS: On day 14, 52.5% of ketorolac patients and 26.5% of vehicle patients had an summed ocular inflammation score of 0 (P < .001). On day 1, 72.4% of ketorolac patients and 39.7% of vehicle patients had a pain score of 0 (P < .001). Median time to pain resolution was 1 day in the ketorolac group and 2 days in the vehicle group (P < .001). The percentage of ketorolac and vehicle patients who had a +3-line or more improvement in best-corrected visual acuity from baseline was 60.5% versus 44.0% on day 14 (P = .002). Overall, adverse events were more prevalent in the vehicle group than in the ketorolac group (48.5% vs 35.2%; P = .004). Burning or stinging (per a composite Medical Dictionary for Regulatory Activities) was reported by 1.5% of ketorolac patients and 0.6% of vehicle patients. CONCLUSIONS: Twice-daily ketorolac 0.45% was well tolerated and effectively treated inflammation and pain following cataract surgery.

Acute conjunctivitis: truth and misconceptions.

OBJECTIVE: Acute conjunctivitis is an extremely common condition and can be associated with significant morbidity and economic burden. Despite this, considerable controversy exists pertaining to the prevalence, diagnosis, management, and treatment of the condition. A panel of ophthalmology experts was assembled to review and discuss the current evidence based literature as it pertains to each of these persistent controversies. METHODS AND SCOPE: An acute conjunctivitis round table symposium was convened at the American Academy of Ophthalmology meeting in Atlanta, November 2008. The expert panelists consisted of four academic ophthalmologists in the field of cornea and external disease, whose discussion was informed by an English language literature survey carried out on the PubMed database for the period of January 1972 to October 2008. A narrative summary was generated from the literature review and direct transcription of this event, from which this Review article was developed. FINDINGS AND CONCLUSIONS: Considerable light has been shed on acute microbial conjunctivitis and especially those cases caused by adenovirus. Many of the myths that have perpetuated for years have been debunked by emerging evidence. The advent and the implementation of better diagnostic tools and anti-viral medications will help clinicians to improve their diagnostic accuracy, improve management and treatment decisions, and ultimately benefit patients while saving overall healthcare costs.

Ocular TRUST: nationwide antimicrobial susceptibility patterns in ocular isolates.

PURPOSE: Ocular Tracking Resistance in U.S. Today (TRUST) annually evaluates in vitro antimicrobial susceptibility of Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae to ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, penicillin, azithromycin, tobramycin, trimethoprim, and polymyxin B in national samples of ocular isolates. DESIGN: Laboratory investigation. METHODS: Prospectively collected ocular isolates (197 S. aureus, 49 S. pneumoniae, and 32 H. influenzae) from 35 institutions and archived ocular isolates (760 S. pneumoniae and 356 H. influenzae) from 34 institutions were tested by an independent, central laboratory. Mean minimum inhibitory concentrations that would inhibit growth of 90% of the tested isolates (MIC(90)) were interpreted as susceptible, intermediate, or resistant according to standardized breakpoints for systemic treatment. S. aureus isolates were classified as methicillin susceptible (MSSA) or methicillin resistant (MRSA). RESULTS: MSSA or MRSA susceptibility patterns were virtually identical for the fluoroquinolones, that is, MSSA susceptibility was 79.9% to 81.1% and MRSA susceptibility was 15.2%. Trimethoprim was the only agent tested with high activity against MRSA. All S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; 89.8% were susceptible to ciprofloxacin. H. influenzae isolates were 100% susceptible to all tested agents but trimethoprim. Ocular TRUST 1 data were consistent with the eight-year longitudinal sample of archived ocular isolates. CONCLUSIONS: The fluoroquinolones were consistently active in MSSA, S. pneumoniae, and H. influenzae. After more than a decade of intensive ciprofloxacin and levofloxacin use as systemic therapy, 100% of ocular S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; nonsusceptibility to ciprofloxacin was less than 15%. High-level in vitro MRSA resistance suggests the need to consider alternative therapy to fluoroquinolones when MRSA is a likely pathogen.

Vernal conjunctivitis.

Vernal conjunctivitis is a bilateral, seasonal, external ocular inflammatory disease of unknown cause. Afflicted patients experience intense itching, tearing, photophobia, and mucous discharge, and usually demonstrate large cobblestone papillae on their superior tarsal conjunctiva and limbal conjunctiva. It primarily affects children, may be related to atopy, and has environmental and racial predilections. Although usually self-limited, vernal conjunctivitis can result in potentially blinding corneal complications. Treatment of chronic forms of ocular allergies may necessitate collaborative efforts between the ophthalmologist and the allergist or immunologist.

Diagnosis of limited ophthalmic Wegener granulomatosis: distinctive pathologic features with ANCA test confirmation.

PURPOSE: To describe the clinical and histopathologic finding of very limited ophthalmic Wegener granulomatosis (WG). METHODS: Thirteen patients with scleritis, orbitopathy, episcleritis, and panuveitis were studied. They presented without evidence of lung or kidney disease, though eight had sinus involvement. We reviewed the biopsies for histopathologic findings consistent with WG, and tested for antineutrophil cytoplasmic antibodies antineutrophil cytoplasmic antibody (ANCA). RESULTS: WG was suggested by granulomatous foci, collagen necrosis, neutrophils/nuclear dust, plasma cells and infiltrating eosinophils. Granular degeneration of the interstitial collagen; mummification of the collagen with disappearance of fibroblastic nuclei; and a polymorphous infiltrate exhibiting plasma cells, lymphocytes, neutrophils, and eosinophils within the epithelioid granulomas should suggest the diagnosis. ANCA test results supported the diagnosis of WG in all cases. CONCLUSION: The described histologic characteristics are highly suggestive of WG. These findings along with clinical or laboratory findings, allow the diagnosis of very limited ophthalmic WG in the absence of systemic involvement.

Double-masked study of the effects of nepafenac 0.1% and ketorolac 0.4% on corneal epithelial wound healing and pain after photorefractive keratectomy.

Two NSAIDs--nepafenac 0.1% and ketorolac tromethamine 0.4%-were compared in terms of their effects on corneal reepithelialization and pain after photorefractive keratectomy (PRK) in a randomized, double-masked, contralateral eye, multicenter study. A total of 40 healthy adult patients who were undergoing sequential bilateral PRK received nepafenac 0.1% and ketorolac 0.4% in contralateral eyes, 1 drop 3 times daily for 3 d after bandage contact lens insertion. Patients were assessed on postoperative days 1, 3, 4, 5, and 7. At each visit, patients provided a general rating of pain. Each patient also assessed the sensation of each eyedrop following instillation (after-drop pain, irritation, burning/stinging, and overall comfort). Starting on day 3, epithelial defect size was assessed. Mean epithelial defect size was similar between treatments at each postoperative visit (P>.05). The average time-to-healing was 4.18 d for nepafenac 0.1% and 4.00 d for ketorolac 0.4% (P=.3134). No statistical difference was observed between nepafenac 0.1% and ketorolac 0.4% in mean postoperative pain scores (P>.05). On day 3, the nepafenac 0.1% group had significantly lower mean sensation scores than did the ketorolac 0.4% group for after-drop pain (P=.0090), irritation (P=.0007), and burning/ stinging (P=.0003). Mean overall comfort score was also significantly better for nepafenac 0.1% on day 3 (7.43 vs 6.41; P<.0001). Nepafenac 0.1% and ketorolac 0.4% provide postoperative pain relief after PRK surgery without associated adverse effects on corneal epithelial healing. Nepafenac 0.1% treatment may offer greater comfort upon instillation in patients who have undergone PRK.

Clinical comparison of two topical prednisolone acetate 1% formulations in reducing inflammation after cataract surgery.

PURPOSE: To compare the efficacy of two formulations of prednisolone acetate 1% in reducing postoperative inflammation in patients having primary phacoemulsification surgery with IOL implantation. METHODS: This multicenter study was conducted in randomized, double-masked fashion with a parallel active control group. Patients undergoing phacoemulsification surgery with IOL implantation were assigned to one of two treatment groups receiving study drug in addition to standard therapy. Study drug was administered four times daily beginning one day before surgery, postoperatively for 14 days, then twice daily until the bottle was empty. Clinical efficacy was compared for differences in corneal surface keratitis, anterior chamber cells and flare, and postoperative pain. Results were compared on day 1, 2 weeks, and 4 weeks postoperatively. RESULTS: No statistical differences in clinical efficacy or safety were seen between the two formulations tested at any time point evaluated. CONCLUSIONS: In this study of routine cataract patients, both prednisolone acetate 1% formulations are comparably effective and safe when administered for the reduction of inflammation after phacoemulsification surgery with IOL implantation.

Anterior segment and external ocular disorders associated with human immunodeficiency virus disease.

The eye is a common site for complications of human immunodeficiency virus (HIV) infection. Although cytomegalovirus retinitis remains the most prevalent of the blinding ocular disorders that can occur in individuals with the acquired immunodeficiency syndrome (AIDS), several important HIV-associated disorders may involve the anterior segment, ocular surface, and adnexae. Some of these entities, such as Kaposi sarcoma, were well described, but uncommon, before the HIV epidemic. Others, like microsporidial keratoconjunctivitis, have presentations that differ between affected individuals with HIV disease and those from the general population who are immunocompetent. The treatment of many of these diseases is challenging because of host immunodeficiency. Survival after the diagnosis of AIDS has increased among individuals with HIV disease because of more effective antiretroviral therapies and improved prophylaxis against, and treatment of, opportunistic infections. This longer survival may lead to an increased prevalence of anterior segment and external ocular disorders. In addition, the evaluation and management of disorders such as blepharitis and dry eye, which were previously overshadowed by more severe, blinding disorders, may demand increased attention, as the general health of this population improves. Not all individuals infected with HIV receive potent antiretroviral therapy, however, because of socioeconomic or other factors, and others will be intolerant of these drugs or experience drug failure. Ophthalmologists must, therefore, still be aware of the ocular findings that develop in the setting of severe immunosuppression. This article reviews the spectrum of HIV-associated anterior segment and external ocular disorders, with recommendations for their evaluation and management.

Visual prosthetic device for bilateral end-stage macular degeneration.

Age-related macular degeneration is the leading cause of blindness in the USA. For the 1.8 million patients in the most advanced stages, there are currently no available treatments to improve vision. A visual prosthetic device that provides one eye with an enlarged retinal image of the central visual field has been developed with the goal of improving central vision in patients with bilateral end-stage macular degeneration. The other eye is left unimplanted to provide peripheral vision. This device is designed for implantation in the posterior chamber of the eye during an outpatient surgical procedure. In US Food and Drug Administration clinical trials, 72% of patients experienced an improvement in their level of visual impairment (profound or severe, to severe or moderate). This was accompanied by a clinically significant improvement in quality of life.