David A. Hollander

Dexamethasone Intravitreal Implant in Combination with Laser Photocoagulation for the Treatment of Diffuse Diabetic Macular Edema

PURPOSE To evaluate Ozurdex (dexamethasone intravitreal implant [DEX implant]; Allergan, Inc, Irvine, CA) 0.7 mg combined with laser photocoagulation compared with laser alone for treatment of diffuse diabetic macular edema (DME). DESIGN Randomized, controlled, multicenter, double-masked, parallel-group, 12-month trial. PARTICIPANTS Two hundred fifty-three patients with retinal thickening and impaired vision resulting from diffuse DME in at least 1 eye (the study eye) were enrolled. INTERVENTION Patients were randomized to treatment in the study eye with DEX implant at baseline plus laser at month 1 (combination treatment; n = 126) or sham implant at baseline and laser at month 1 (laser alone; n = 127) and could receive up to 3 additional laser treatments and 1 additional DEX implant or sham treatment as needed. MAIN OUTCOME MEASURES The primary efficacy variable was the percentage of patients who had a 10-letter or more improvement in best-corrected visual acuity (BCVA) from baseline at month 12. Other key efficacy variables included the change in BCVA from baseline and the area of vessel leakage evaluated with fluorescein angiography. Safety variables included adverse events and intraocular pressure (IOP). RESULTS The percentage of patients who gained 10 letters or more in BCVA at month 12 did not differ between treatment groups, but the percentage of patients was significantly greater in the combination group at month 1 (P<0.001) and month 9 (P = 0.007). In patients with angiographically verified diffuse DME, the mean improvement in BCVA was significantly greater with DEX implant plus laser treatment than with laser treatment alone (up to 7.9 vs. 2.3 letters) at all time points through month 9 (P ≤ 0.013). Decreases in the area of diffuse vascular leakage measured angiographically were significantly larger with DEX implant plus laser treatment through month 12 (P ≤ 0.041). Increased IOP was more common with combination treatment. No surgeries for elevated IOP were required. CONCLUSIONS There was no significant between-group difference at month 12. However, significantly greater improvement in BCVA, as demonstrated by changes from baseline at various time points up to 9 months and across time based on the area under the curve analysis, occurred in patients with diffuse DME treated with DEX implant plus laser than in patients treated with laser alone. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Drug-induced corneal complications.

Purpose of review To review the common corneal manifestations of systemic medications in order to describe the characteristic clinical features associated with particular systemic drugs, the indications for drug cessation, and the risks for irreversible ocular toxicity. Recent findings Systemic medications may reach the cornea via the tear film, aqueous humor, and limbal vasculature. The corneal changes are often the result of the underlying chemical properties of medications. Amphiphilic medications (amiodarone, chloroquine, suramin, clofazimine, etc.) may produce a drug-induced lipidosis and development of a vortex keratopathy. Antimetabolites (cytarabine) may lead to a degeneration of basal epithelial cells with formation of epithelial microcysts. Additionally, systemically administered medications and drug metabolites may lead to a stromal or endothelial deposition. Corneal changes may result in reduced visual acuity, photophobia, and ocular irritation, though these symptoms typically resolve following drug cessation. Corneal manifestations of systemic medications are often dose related, and may reflect the potential risk for lenticular or retinal changes. Summary Corneal changes secondary to systemic medications may affect all layers of the cornea. While corneal deposition is typically not an indication for drug cessation, patients receiving particular medications should be monitored for symptoms related to corneal deposition as well as for signs of irreversible ocular toxicity.

Efficacy and safety of two or more dexamethasone intravitreal implant injections for treatment of macular edema related to retinal vein occlusion (Shasta study).

Purpose: To evaluate the efficacy, safety, and reinjection interval of dexamethasone intravitreal implant (DEX implant) in branch retinal vein occlusion and central retinal vein occlusion patients receiving ≥2 DEX implant treatments. Methods: Multicenter (26-site), retrospective chart review study. Data were collected from baseline (at first DEX implant) through 3 months to 6 months after last DEX implant. Results: Patients (n = 289) received 2 to 9 (mean, 3.2) DEX implants as monotherapy (29.1% of patients) or with adjunctive treatments/procedures. Mean duration of macular edema before first DEX implant was 18.4 months. Mean reinjection interval was 5.6 months. Mean peak change in best-corrected visual acuity from baseline through 4 weeks to 20 weeks after final DEX implant was +1.0 line (P < 0.001). Best-corrected visual acuity and central retinal thickness improved significantly from baseline after each of the first 6 DEX implant injections (P ⩽ 0.037); 59.7% of branch retinal vein occlusion and 66.7% of central retinal vein occlusion patients achieved ≥2-line best-corrected visual acuity improvement. Intraocular pressure increase (≥10 mmHg) occurred in 32.6% of patients; 29.1% used intraocular pressure-lowering medication to treat increases associated with DEX implant. Only 1.7% of patients required incisional glaucoma surgery. Conclusion: Retinal vein occlusion patients treated with multiple DEX implant injections, either alone or combined with other therapies, had improved central retinal thickness and visual acuity with each subsequent injection. No new safety concerns developed with multiple implants.

Ahmed Valve Implantation with Adjunctive Mitomycin C and 5-Fluorouracil: Long-term Outcomes

PURPOSE To evaluate long-term outcomes after Ahmed valve implantation in patients with glaucoma when using adjunctive intraoperative mitomycin C (MMC) and postoperative 5-fluorouracil (5-FU). DESIGN Retrospective, interventional, consecutive case series. METHODS A consecutive series of eyes undergoing Ahmed valve implantation, either alone (AHMED eyes) or in combination with cataract surgery (AHMED+PHACO), using both intraoperative MMC and postoperative 5-FU were evaluated. Failure was defined as the first occurrence of any of the following: 1) the first of three consecutive visits where intraocular pressure (IOP) was >18 mm Hg or <20% IOP reduction from baseline and the final number of topical medications was not reduced by at least two from baseline, 2) the need for additional surgery, or 3) the development of serious complications. RESULTS A total of 130 eyes underwent Ahmed valve implantation with intraoperative exposure to 0.5 mg/ml MMC (median time: eight minutes; range, four to 10) and postoperative subconjunctival injections of 5 mg of 5-FU (median: five injections; range, zero to nine). Kaplan-Meier estimates of the cumulative probability of valve success and confidence interval (CI) at the sixth follow-up year were 0.72 (95% CI, 0.59 to 0.82) for AHMED eyes (n = 88), 0.84 (95% CI, 0.65 to 0.93) for AHMED+PHACO eyes (n = 42). A median of two fewer medications were required relative to baseline for both AHMED and AHMED+PHACO eyes. CONCLUSIONS The adjunctive use of both intraoperative MMC and postoperative 5-FU with Ahmed valve implantation results in high success rates. IOP was well controlled in the majority of patients within the six-year postoperative period.

SPONTANEOUS CORNEAL HYDROPS AND PERFORATION IN KERATOCONUS AND PELLUCID MARGINAL DEGENERATION

Purpose. To report two cases of pellucid marginal degeneration and one case of keratoconus associated with spontaneous corneal hydrops leading either to perforation or imminent perforation, requiring urgent keratoplasty. Method. Retrospective interventional case series of three patients with noninflammatory peripheral corneal degenerations. A retrospective review was done of the clinical courses, surgical interventions, and pathologic specimens, development of spontaneous hydrops, perforation, need for surgical intervention, and final visual outcome. Results. Two patients with pellucid marginal degeneration and one with keratoconus developed spontaneous hydrops followed by aqueous leakage through markedly thinned anterior stroma. In one case, the leak site was successfully sealed after three separate applications of tissue adhesive, although the remaining two cases required penetrating keratoplasty. Conclusions. These cases document the very unusual occurrence of corneal hydrops leading to spontaneous corneal perforation in patients with keratoconus and pellucid marginal degeneration.

LATE-ONSET TRAUMATIC FLAP DISLOCATION AND DIFFUSE LAMELLAR INFLAMMATION AFTER LASER IN SITU KERATOMILEUSIS

Purpose. To report a case of traumatic flap partial dislocation and subsequent diffuse lamellar inflammation 14 months after laser in situ keratomileusis (LASIK) retreatment. Methods. Case report of a late flap dislocation that occurred during routine recreational activity (struck with a finger in the right eye while playing basketball). Results. The partially dislocated LASIK flap was reflected nasally, and the stromal surfaces of the flap and bed were thoroughly scraped to remove debris and epithelial cells. The flap was repositioned, and a bandage contact lens was placed. Diffuse lamellar inflammation, which developed on post-trauma day number two, was successfully treated with frequent topical steroids. Three weeks after the injury, the patient had regained 20/20 uncorrected visual acuity. Conclusions. Patients should be appropriately warned of the possibility of late flap dislocation with traumatic forces encountered during routine recreational activities. Full visual recovery is possible if the dislocation is promptly diagnosed and appropriately managed.

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.

Three-month, randomized, parallel-group comparison of brimonidine–timolol versus dorzolamide–timolol fixed-combination therapy

ABSTRACT Objective: Fixed combinations of 0.2% brimonidine–0.5% timolol and 2% dorzolamide–0.5% timolol are used to lower intraocular pressure (IOP). The objective of this study was to evaluate the IOP-lowering efficacy and ocular tolerability of brimonidine–timolol compared with dorzolamide–timolol when used as monotherapy or as adjunctive therapy to a prostaglandin analog (PGA) in patients with glaucoma or ocular hypertension. Study design and methods: Pooled data analysis of two randomized, investigator-masked, 3-month, parallel-group studies with identical protocols (ten sites). In all, 180 patients with open-angle glaucoma or ocular hypertension who were in need of lower IOP received topical brimonidine–timolol BID or dorzolamide–timolol BID as monotherapy (n = 101) or as adjunctive therapy to a PGA (latanoprost, bimatoprost, or travoprost) (n = 79). Clinical trial registration: The studies are registered with the identifiers NCT00822081 and NCT00822055 at http://www.clinicaltrials.gov. Main outcome measures: IOP was measured at 10 a.m. (peak effect) at baseline and at months 1 and 3. Tolerability/comfort was evaluated using a patient questionnaire. Results: There were no statistically significant between-group differences in patient demographics. Most patients were Caucasian, and the mean age was 68 years. There were also no statistically significant differences between treatment groups in baseline IOP. At month 3, the mean (SD) reduction from baseline IOP for patients on fixed-combination monotherapy was 7.7 (4.2) mmHg (32.3%) with brimonidine–timolol versus 6.7 (5.0) mmHg (26.1%) with dorzolamide–timolol (p = 0.040). The mean reduction from PGA-treated baseline IOP for patients on fixed-combination adjunctive therapy was 6.9 (4.8) mmHg (29.3%) with brimonidine–timolol versus 5.2 (3.7) mmHg (23.5%) with dorzolamide–timolol (p = 0.213). Patients on brimonidine–timolol reported less burning (p < 0.001), stinging (p < 0.001), and unusual taste (p < 0.001) than patients on dorzolamide–timolol. Conclusions: Fixed-combination brimonidine–timolol provided the same or greater IOP lowering compared with fixed-combination dorzolamide–timolol. Both fixed-combination medications were safe and well-tolerated. Brimonidine–timolol received higher ratings of ocular comfort than dorzolamide–timolol. The duration of the studies was 3 months, and additional studies will be needed to compare the efficacy and tolerability of brimonidine–timolol and dorzolamide–timolol during long-term treatment.

Graft Failure After Penetrating Keratoplasty in Eyes With Ahmed Valves

PURPOSE To determine incidence and risk factors for graft failure following penetrating keratoplasty (PK) in eyes with Ahmed valves (AV). DESIGN Retrospective, observational cohort study. METHODS Patients who underwent PK after AV implantation (both performed at our institution through 2004) were studied. Intervals to graft failure (defined as either dysfunction [stromal thickening with retention of clarity] or decompensation [central microcystic edema or loss of clarity]) were analyzed using Kaplan-Meier technique. Risk factors for graft failure were analyzed using Cox proportional hazard models. RESULTS Included were 77 eyes (77 patients; first procedure 1993). Following PK, 40 eyes (52%) required increased numbers of glaucoma medications; 10 eyes (13%) required additional glaucoma drainage device(s). Graft failure at 1, 2, and 3 years was 42.4% (95% confidence interval: 32.0%-54.6%), 57.1% (45.6%-69.1%), and 59.1% (47.5%-71.2%), respectively. Prior PK (HR 2.38, P = .006) and stromal vessels (HR 2.90, P = .0005) were associated with increased risk of graft failure. Use of glaucoma medications (HR 0.27, P = .009) and evidence of lower intraocular pressures (IOP) during follow-up (excluding hypotony; HR 0.92, P = .010) were associated with reduced risk of graft failure. Endothelial rejection episodes were observed in 13 eyes (17%); however, rejection was not a risk factor for graft failure (P = .98). CONCLUSIONS Long-term survival of corneal grafts is poor in eyes with AV. The majority of graft failures are associated with progressive loss of endothelial function, without observed immunologic rejection. Despite the presence of an AV, escalation in glaucoma therapy often follows PK; graft failure may be related to poor IOP control.

Methicillin resistance of Staphylococcus species among health care and nonhealth care workers undergoing cataract surgery

Purpose: The purpose of this study is to characterize the bacterial flora of the ocular and periocular surface in cataract surgery patients and to determine the prevalence of methicillin resistance among staphylococcal isolates obtained from health care workers (HCWs) and non-HCWs. Methods: In this prospective, multicenter, case series study, eyelid and conjunctival cultures were obtained from the nonoperative eye of 399 consecutive cataract patients on the day of surgery prior to application of topical anesthetics, antibiotics, or antiseptics. Speciation and susceptibility testing were performed at the Dean A. McGee Eye Institute. Logistic regression was utilized to evaluate whether any factors were significant in predicting the presence of methicillin-resistant staphylococcal isolates. Results: Staphylococcus epidermidis (62.9%), followed by S. aureus (14.0%), was the most frequently isolated organism. Methicillin-resistant S. epidermidis accounted for 47.1% (178/378) of S. epidermidis isolates, and methicillin-resistant S. aureus accounted for 29.5% (26/88) of S. aureus isolates. Methicillin-resistant staphylococcal isolates were found in 157 of 399 (39.3%) patients, the majority (89.2%) of whom were non-HCWs. The likelihood of being colonized with methicillin-resistant organisms increased with age (odds ratio [OR], 1.27; 95% confidence interval [CI]: 1.02–1.58; P = 0.04) but decreased with diabetes (OR, 0.51; 95% CI: 0.29–0.89; P = 0.02). Being a HCW (OR, 1.25; 95% CI: 0.61–2.58; P = 0.54) was not a risk factor for colonization with methicillin-resistant organisms. Conclusion: Patients without exposure to health care environments are as likely as HCWs to be colonized with methicillin-resistant organisms. Increasing methicillin resistance with age may partially explain the increased risk of endophthalmitis reported with older age.