Risk factors for herpes simplex virus epithelial keratitis recurring during treatment of stromal keratitis or iridocyclitis. Herpetic Eye Disease Study Group.

AIMS: Possible risk factors were evaluated for herpes simplex virus (HSV) epithelial keratitis in patients with stromal keratouveitis. METHODS: The study population included 260 patients who had active stromal keratitis and/or iridocyclitis without epithelial disease and who were enrolled in one of three clinical trials of the Herpetic Eye Disease Study. Study treatment involved a 10 week course of topical placebo, topical prednisolone phosphate, or topical prednisolone phosphate with oral acyclovir. All groups received topical trifluridine four times daily for 3 weeks then twice daily for another 7 weeks. Patients were examined for HSV epithelial keratitis for 16 weeks. RESULTS: Dendritic or geographic epithelial keratitis occurred in 12 (4.6%) study patients. Adverse effects attributable to trifluridine prophylaxis were acute allergic blepharoconjunctivitis in 10 (3.8%) study patients and corneal epithelial erosions in 11 (4.2%) study patients. No significant difference in the occurrence of HSV epithelial keratitis was found among the study treatment groups: one (2.0%) of 49 topical placebo treated patients, nine (6.5%) of 138 patients treated with topical corticosteroids without acyclovir, and two (2.7%) of 73 patients treated with topical corticosteroids and oral acyclovir. Univariate exponential models suggested that patients with a history of previous HSV epithelial keratitis and non-white patients were more likely to develop HSV epithelial keratitis during treatment of stromal keratouveitis. CONCLUSION: Individuals with prior HSV epithelial keratitis and certain ethnic groups may have a higher rate of recurrent epithelial keratitis during the acute treatment of HSV stromal keratouveitis.

Comparison of ciprofloxacin ophthalmic solution 0.3% to fortified tobramycin-cefazolin in treating bacterial corneal ulcers. Ciprofloxacin Bacterial Keratitis Study Group.

PURPOSE: The purpose of the study is to compare the clinical efficacy and safety of ciprofloxacin ophthalmic solution 0.3% (Ciloxan) with a standard therapy regimen (fortified tobramycin, 1.3%-cefazolin, 5.0%) for treating bacterial corneal ulcers. METHODS: This randomized, parallel group, double-masked, multicenter study was conducted in 324 patients at 28 centers in the United States, Europe, and India. Patients were randomized into 2 treatment groups: 160 to ciprofloxacin and 164 to fortified tobramycin-cefazolin. Positive microbiologic cultures were obtained in 188 (58%) of 324 patients. Of these, 176 patients met protocol criteria and were evaluated for treatment efficacy: 82 in the ciprofloxacin group and 94 in the standard therapy group. The dosing schedule for both treatment groups was 1 to 2 drops of the first study medication (ciprofloxacin or fortified tobramycin) every 30 minutes for 6 hours, then hourly for the remainder of day 1; 1 to 2 drops every hour on days 2 and 3; 1 to 2 drops every 2 hours on days 4 and 5, followed by 1 to 2 drops every 4 hours on days 6 to 14. The second medication (ciprofloxacin or cefazolin) was instilled 5 to 15 minutes after the first drug, following the same dosing frequency. Physician's judgment of clinical success, cure rate, changes in ocular sings, and symptoms and the rate of treatment failures were the primary efficacy criteria. RESULTS: Topical ciprofloxacin monotherapy is equivalent clinically and statistically to the standard therapy regimen of fortified antibiotics. No statistically significant treatment differences were found between ciprofloxacin (91.5%) and standard therapy (86.2%) in terms of overall clinical efficacy (P = 0.34). Similarly, no differences were noted in resolution of the clinical signs and symptoms (P > 0.08) or the time to cure (P = 0.55). The incidence of treatment failures was less in the ciprofloxacin group (8.5%) compared with the standard therapy group (13.8%). Significantly fewer patients treated with ciprofloxacin reported discomfort than did patients treated with the standard therapy regimen (P = 0.01). CONCLUSION: Ciprofloxacin ophthalmic solution 0.3% monotherapy is equivalent clinically and statistically to standard therapy (fortified tobramycin-cefazolin) for the treatment of bacterial corneal ulcers and produces significantly less discomfort.

Herpetic Eye Disease Study. A controlled trial of oral acyclovir for herpes simplex stromal keratitis.

PURPOSE: To evaluate the efficacy of oral acyclovir in treating stromal keratitis caused by herpes simplex virus (HSV) in patients receiving concomitant topical corticosteroids and trifluridine. METHODS: The authors performed a randomized, double-masked, placebo-controlled, multicenter trial in 104 patients with HSV stromal keratitis without accompanying HSV epithelial keratitis. Sample size was chosen so that a 5%, one-tailed test would have an 80% chance of detecting a doubling of the median time to treatment failure. Patients were randomized to receive a 10-week course of either oral acyclovir (400 mg 5 times daily, n = 51) or placebo (n = 53). All patients also received a standard regimen of topical prednisolone phosphate and trifluridine. Ophthalmologic examinations were performed weekly during the 10-week treatment period, every 2 weeks for an additional 6 weeks, and at 6 months after entry into the trial. RESULTS: The median time to treatment failure (defined as worsening or no improvement of stromal keratitis or an adverse event) was 84 days (95% confidence interval, 69-93 days) for the acyclovir group and 62 days (95% confidence interval, 57-90 days) for the placebo group. By 16 weeks, 38 patients (75%) in the acyclovir group and 39 patients (74%) in the placebo group had failed treatment. Also by that time, the keratitis had resolved with trial medications, and there was no subsequent worsening in nine patients (18%) in the acyclovir group and ten (19%) in the placebo group. None of these results were significantly different between the two groups. However, visual acuity improved over 6 months in significantly more patients in the acyclovir group than in the placebo group. CONCLUSION: There was no statistically or clinically significant beneficial effect of oral acyclovir in treating HSV stromal keratitis in patients receiving concomitant topical corticosteroids and trifluridine with regard to time to treatment failure, proportion of patients who failed treatment, proportion of patients whose keratitis resolved, time to resolution, or 6-month best-corrected visual acuity. Visual acuity improved over 6 months in more patients in the acyclovir group than in the placebo group.

Herpetic Eye Disease Study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis.

PURPOSE: To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis. METHODS: The authors performed a randomized, double-masked, placebo-controlled, multicenter clinical trial of 106 patients with active herpes simplex stromal keratitis who had not received any corticosteroids for at least 10 days before study enrollment. Patients were assigned to the placebo group (n = 49) or the steroid group (topical prednisolone phosphate; n = 57); both regimens were tapered over 10 weeks. Both groups received topical trifluridine. Visual acuity assessment and slit-lamp biomicroscopy were performed weekly for 10 weeks, every other week for an additional 6 weeks or until removal from the trial, and at 6 months after randomization. RESULTS: The time to treatment failure (defined by specific criteria as persistent or progressive stromal keratouveitis or an adverse event) was significantly longer in the steroid group compared with the placebo group. Compared with placebo, corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%. The time from randomization to resolution of stromal keratitis and uveitis was significantly shorter in the steroid group compared with the placebo group even though both groups included patients who were removed from the study and treated with topical corticosteroids according to best medical judgment. Nineteen (33%) of the steroid-treated patients and 11 (22%) of the placebo-treated patients completed the 10 weeks of protocol therapy and had stable, noninflamed corneas after 16 weeks. At 6 months after randomization, no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease were identified between the steroid and placebo groups. CONCLUSIONS: The topical corticosteroid regimen used in this study was significantly better than placebo in reducing persistence or progression of stromal inflammation and in shortening the duration of herpes simplex stromal keratitis. Postponing steroids during careful observation for a few weeks delayed resolution of stromal keratitis but had no detrimental effect as assessed by visual outcome at 6 months.

Penetrating keratoplasty and intraocular lens exchange: open-loop anterior chamber lenses versus sutured posterior chamber lenses.

Penetrating keratoplasty with intraocular lens (IOL) exchange is generally recommended for eyes with pseudophakic bullous keratopathy, especially when the keratopathy is associated with uveitis, chronic cystoid macular edema, or a uveitis-glaucoma-hyphema syndrome. Review of the literature has shown basically equivalent long-term results of penetrating keratoplasty and IOL exchange using both Kelman-style, flexible, open-loop anterior chamber lenses and acapsular fixation of sutured posterior chamber lenses. The use of suture-fixated posterior chamber IOLs appears warranted in centers where the surgeon has extensive experience with this specific technique and in cases with special indications, for example, in eyes with extensive angle abnormalities. However, because this technique is more difficult to perform, and in the absence of such preexisting contraindications, for most practices we do not hesitate to recommend the use of a Kelman-style anterior chamber lens during routine cases of penetrating keratoplasty and IOL exchange.

Trabeculectomy for traumatic hyphema with increased intraocular pressure.

We reviewed the medical records of 11 consecutive patients who underwent trabeculectomy with anterior chamber washout and peripheral iridectomy as the primary surgical treatment for traumatic hyphema that was unresponsive to medical management. The mean intraocular pressure before surgery was 48 mm Hg. In ten of the patients the intraocular pressure was lowered to 21 mm Hg or lower after surgery and remained below that level up to the most recent follow-up visit, which ranged from eight to 97 months. One patient required a topical beta-blocker and oral acetazolamide to lower pressure to this level after surgery. Eight patients had visual acuity of 20/60 or better at last follow-up. Corneal blood staining occurred in eight patients. Compared with other techniques for surgical management of traumatic hyphema, trabeculectomy provides a means to keep intraocular pressure lowered while the remaining blood is clearing from the anterior chamber. Trabeculectomy with anterior chamber washout and peripheral iridectomy appears to be a safe and reliable procedure in the management of traumatic hyphemas in which medical management fails to control intraocular pressure.

0.3% ciprofloxacin ophthalmic ointment in the treatment of bacterial keratitis. The Ciprofloxacin Ointment/Bacterial Keratitis Study Group.

OBJECTIVE: To determine the efficacy and safety of topical 0.3% ciprofloxacin hydrochloride ophthalmic ointment in the treatment of bacterial keratitis. DESIGN: Prospective case series with a nonrandomized comparison of culture-positive, evaluable cases (ciprofloxacin ointment group) with culture-positive, concurrent patients (nonenrolled group) treated with conventional therapy. SETTING: Multicenter clinical study. PATIENTS: After informed consent was obtained, 253 eligible patients underwent corneal scrapings and received topical ciprofloxacin ointment; 145 (57%) had positive cultures and completed the follow-up schedule. Forty (70%) of 57 apparently eligible patients had culture-positive bacterial keratitis but were not enrolled in the ciprofloxacin ointment study during the same period. INTERVENTION: Ciprofloxacin ophthalmic ointment instilled every 1 to 2 hours for 2 days, then every 4 hours for 12 days. MAIN OUTCOME MEASURES: Clinical evaluation of signs at 1, 3, 7, and 14 days of treatment and the overall condition classified as clinical success (cured or improved) or failure (unchanged or worse) during and after therapy. RESULTS: Clinical success with the initial treatment occurred in 135 patients (93%) in the ciprofloxacin ointment group and in 28 patients (70%) in the nonenrolled group. Of the 10 ciprofloxacin clinical failures, seven were staphylococcal; two, pneumococcal; and one, polybacterial. The 90% minimum inhibitory concentration of ciprofloxacin was 3 mg/L or less for corneal bacterial isolates. No serious adverse event attributable to ciprofloxacin ointment occurred, although 32 (13%) of 253 patients developed a transient white crystalline corneal precipitate shown with liquid chromatography in two cases to be ciprofloxacin. CONCLUSION: Ciprofloxacin ophthalmic ointment is an effective and safe topical antimicrobial agent for the treatment of bacterial keratitis caused by susceptible microorganisms.

Contact lens-related infectious keratitis.

Infectious keratitis is the most serious complication of contact lens use. Virtually all contact lens wearers are at risk. Initial therapy consists of frequent broad-spectrum fortified antibiotic drops after appropriate laboratory workup. Pseudomonas and Acanthamoeba species are the most important causes of contact lens-associated ulcers. Acanthamoeba keratitis produces significant ocular morbidity, and treatment is not always effective. Recent studies have provided new insights regarding the incidence, risk factors, and pathogenesis of contact lens-related infectious keratitis. Extended-wear soft contact lens wearers are at greatest risk. With our present understanding of the pathogenesis and risk factors of contact lens-related infectious keratitis, daily-wear schedules are strongly advised. Even under the best of lens care conditions, infectious keratitis may still occur. It is therefore imperative that patients be informed to remove their lenses and seek medical evaluation if any discomfort develops.

Infectious conjunctivitis.

This article is designed to aid the clinician in the diagnosis of bacterial and viral conjunctivitis by evaluating a wide variety of infectious causes of conjunctivitis. The work-up, including techniques of examination and pertinent laboratory studies, is discussed. Clinical features of each type are covered at length and specific therapy for each is included.

Overview of the corneal toxicity of surgical solutions and drugs: and clinical concepts in corneal edema.

Surgical solutions and drugs are important in ocular surgery. These include irrigating solutions, viscoelastic substances, mydriatics and miotics, and a growing number of other agents designed to enhance intraocular surgery and its outcome. Potential for damage to the corneal endothelium and other tissues is related to the chemical composition, pH, and osmolality of the irrigating solutions that bathe tissues. Quality balanced salt solutions (BSS) are usually safe for use as an intraocular solution in patients with normal corneal endothelium. If prolonged irrigation times are expected, or the patient already has decompensated endothelium, i.e., primary or secondary endotheliopathy, the use of a "complete" BSS solution is indicated to minimize damage. Intraocular sulfite-containing epinephrine may cause severe corneal edema and should be avoided, or if used, be well diluted. Sulfite-free epinephrine solution is now available and does not cause the endothelial toxicity that one may see with sulfite-containing epinephrine solutions. Current formulations of acetylcholine and carbachol used as miotics in surgery have been evaluated in humans and caution is recommended in using acetylcholine solutions intracamerally in patients with already decompensated endothelium. Chondroitin sulfate, hydroxypropyl methylcellulose, and sodium hyaluronate are non-toxic to animal endothelial cells under conditions analogous to cataract extraction in humans but can be toxic to endothelium if there is continued contact with endothelium for hours. Chondroitin sulfate has been shown to have more of a protective effect in mechanical pseudophakos trauma probably because of its cohesiveness and tendency to coat the endothelium. Viscoelastics cause a significant rise in intraocular pressure of > 30 mm Hg in 3-10% of patients. Very high intraocular pressures are often seen postoperatively after viscoelastic use surgically in patients who preoperatively have a history of ocular hypertension or glaucoma.

The role of viscoelastics, cannulas, and irrigating solution additives in post-cataract surgery corneal edema: a brief review.

Corneal clarity is dependent upon maintenance of the corneal endothelial barrier and pump. Mechanical trauma is usually considered to be the most significant factor in corneal endothelial damage during cataract surgery resulting in postoperative corneal edema. However, corneal decompensation out of proportion to the degree of trauma seen during surgery does occur. These cases of unexpected corneal edema can often be traced to unrecognized preoperative endothelial dysfunction or to toxicity of intraocular medications used during surgery. This paper reviews the role of viscoelastics in reducing surgical trauma, their toxicity, and the risks of toxicity inherent in the use of re-usable cannulas and irrigating solution additives. Disposable cannulas should be used whenever possible. The use of re-usable cannulas with viscoelastics is highly likely to result in toxic residues being introduced onto the eye, and must be avoided. Irrigating solution additives should be tested with in-vitro human donor cornea perfusions prior to clinical use.

Blastomycosis of the eyelid and conjunctiva.

A 37-year-old man with a recurrent papillomatous lesion of the upper eyelid and four separate bulbar conjunctival ulcers was found to have North American blastomycosis. This represents the first reported case with conjunctival lesions that were not simply contiguous with eyelid involvement. This case underscores the importance of considering blastomycosis in the differential diagnosis of granulomatous conjunctivitis and when examining a lesion of the eyelid resembling a squamous cell carcinoma or atypical papilloma.

Insights from experimental data on ciprofloxacin in the treatment of bacterial keratitis and ocular infections.

Ciprofloxacin is a potent fluoroquinolone antibiotic with in vitro activity against many significant gram-positive and gram-negative ocular pathogens. A review of the experimental studies of this antibiotic shows bactericidal activity, a broad antimicrobial spectrum, and a low incidence of resistance. The growing body of experimental data supports the effectiveness of ciprofloxacin in the treatment of experimental keratitis and suggest that it be evaluated further in ocular infections.

Efficacy and safety of mercuric oxide in the treatment of bacterial blepharitis.

A double-masked, placebo-controlled, randomized study was done to assess the safety and clinical and quantitative microbiologic efficacy of 1% mercuric oxide (yellow) ophthalmic ointment in the treatment of eyelid infections, i.e., bacterial blepharitis. A total of 39 patients with bacterial counts and clinical signs indicative of eyelid infection were treated twice daily for 7 days. Clinical biomicroscopic examination and quantitative microbiologic cultures were done just prior to initiation of treatment and again on days 3 and 7. Statistical analysis revealed a significant improvement in the clinical signs, bacterial count, cure rate, and improvement rate for subjects taking the active medication, compared with those taking the placebo on days 3 and 7. In addition, the medication was well tolerated.

Filter-culture technique using amoeba saline transport medium for the noninvasive diagnosis of Acanthamoeba keratitis.

Acanthamoeba, a common free-living amoeba, is increasingly incriminated as a cause of keratitis and corneal ulceration. Between March 1986 and July 1988, specimens from seven patients submitted by ophthalmologists to the City of Milwaukee Health Department's Bureau of Laboratories were culture positive for Acanthamoeba. All patients were contact lens wearers. The specimens were transported at ambient temperature in amoebasaline (5.0 mL) and filtered through 13 mm 0.22 microns cellulose filters. The filters were then plated in cocultivation with Escherichia coli on nonnutrient agar and had positive results for Acanthamoeba in two to five days. Contact lens cases were culture positive for Acanthamoeba in three instances. These results indicate that corneal scraping in amoeba saline transport medium can provide an effective way to diagnose Acanthamoeba keratitis when direct culture of such specimens is not possible.

Penetrating keratoplasty and intraocular lens exchange for pseudophakic bullous keratopathy associated with a closed-loop anterior chamber intraocular lens.

We reviewed the records of 20 consecutive eyes with pseudophakic bullous keratopathy associated with a closed-loop anterior chamber lens that underwent penetrating keratoplasty, total anterior vitrectomy, and anterior chamber intraocular lens exchange. On reexamination, all corneal grafts had remained clear during an average follow-up period of 15 months (range, four to 45 months). Seven eyes (35%) attained a visual acuity of 20/40 or better with spectacle correction; however, 15 of 20 eyes (75%) attained a best-corrected visual acuity of 20/40 or better using a pinhole and a gas-permeable contact lens. In five eyes visual acuity was 20/400 or poorer because of cystoid macular edema, as documented by fluorescein angiography, age-related macular degeneration, or optic atrophy. Localized, minimal peripheral anterior synechiae were present on gonioscopy in seven eyes. The one-piece flexible anterior chamber lens implants used for exchange appeared to be well tolerated in this series of patients.