Evidence-based recommendations for the diagnosis and treatment of neovascular glaucoma.

PURPOSE: To succinctly update information on the pathogenesis, etiology, diagnosis, and treatment of neovascular glaucoma based on a systematic review of available literature and to provide summary recommendations rated for their importance to clinical outcome. CLINICAL RELEVANCE: Neovascular glaucoma is a devastating ocular disease that often results in loss of vision. The current standard of care includes retinal ablation and control of increased intraocular pressure with medical and surgical therapy. LITERATURE REVIEW METHODOLOGY: The authors conducted a MEDLINE literature search of articles published in English from 1966 to the present. Each article reviewed was rated as to the strength of evidence it provided, and summary ratings for the strength of evidence supporting clinical recommendations were generated. RESULTS: Level A (most important to patient outcome) recommendations for the diagnosis of neovascular glaucoma include a high index of suspicion, a full ocular examination including undilated gonioscopy, and pupil examination. In regard to treatment, Level A recommendations include treatment of the underlying disease origin, complete panretinal photocoagulation (if retinal ischemia is a factor), and medical control of both elevated intraocular pressure and inflammation. Level B recommendations (moderately important to patient outcome) encompass glaucoma surgery to control intraocular pressure when medical therapy is unsuccessful, although the ideal surgical procedure is unknown. Currently, trabeculectomy with antimetabolite therapy, aqueous shunt implants, and diode laser cyclophotocoagulation are the preferred surgical treatment options. CONCLUSIONS: The current literature on neovascular glaucoma has few articles that provide strong evidence in support of therapy recommendations (level I). Future research studies are needed to address areas in which the current evidence is moderately strong (level II) or weak, consisting only of a consensus of expert opinion (level III). Whenever practicable, these studies should be prospective, randomized clinical trials.

Needle aspiration and endodiathermy treatment of epithelial inclusion cyst of the iris.

PURPOSE: To report a case of recurrent epithelial inclusion cyst of the iris treated with needle aspiration and endodiathermy. METHODS: Case report. A 27-year-old man with a history of congenital cataracts, congenital nystagmus, cataract surgery in each eye at 3 years of age, and a long-standing iris epithelial cyst presented with decreased vision of 20/400 in the better seeing left eye. The reduced vision was diagnosed secondary to growth of the iris inclusion cyst over the pupil. RESULTS: The iris cyst, which occluded the chamber angle and pupil, was treated with aspiration, separation of the cyst wall from the cornea, and endodiathermy. Twelve months after cyst surgery, no evidence existed of epithelial cyst regrowth. The visual function was significantly improved, although Snellen visual acuity was unchanged at 20/400. CONCLUSION: The minimal invasiveness of needle aspiration and diathermy can result in a satisfactory outcome without undertaking more extensive and invasive surgical treatments for epithelial inclusion cysts of the anterior chamber.

Advances in the management of keratomycosis and Acanthamoeba keratitis.

PURPOSE: In the late 1960s, the management of fungal keratitis was a serious unresolved problem. Little was known of the epidemiology of the disease, and there were no antifungal agents formulated for use in the eye. METHODS: A thorough review of the literature was done back to 1969 on clinical reports and experimental studies for keratomycosis and Acanthamoeba keratitis. RESULTS: Since 1969, through basic and clinical research, the epidemiology of the disease worldwide is better understood. One new topical antifungal agent, natamycin, with efficacy against filamentous fungi has been developed and the pharmacokinetics of topically applied antifungal drops have been explored. Progress has been slow but the prognosis for keratomycosis has immeasurably improved over the period. Acanthamoeba was first recognized as an ocular pathogen in 1973 and was the cause of an epidemic in the 1980s caused by contaminated contact lens, although other risk factors were also identified. At the onset of the epidemic, there was no known treatment. but as a result of intense research efforts, within a few years a well-defined therapeutic approach had been developed that had a significant impact on the prognosis for this initially devastating infection. For both infections, the role of corticosteroids for controlling the inflammation remains controversial, but the place for keratoplasty is now well defined. CONCLUSIONS: Although there has been steady progress in the management of both infections, continued research is the way to define more effective medical and surgical therapy.

Differences in virulence between two Candida albicans strains in experimental keratitis.

PURPOSE: To study the differences in disease caused by two wild-type strains of Candida albicans in a model of contact lens-facilitated keratitis in rabbits. METHODS: Two strains, SC5314 and VE175, were examined. Standardized inocula were placed on the debrided corneal surface of one eye in Dutch belted rabbits and covered with a contact lens. A temporary tarsorrhaphy was opened after 24 hours with removal of the contact lens. Six days later, corneas were photographed and animals killed. Corneas were bisected with one half for quantitative isolate recovery and the other for stromal penetration by hyphae. RESULTS: Strain SC5314 was significantly more virulent. The mean hyphal penetration into the cornea was 24.4% +/- 8.5% of the corneal thickness, and in three of six corneas hyphae penetrated through the entire cornea. In contrast, for VE175, the mean hyphal penetration was 2.6% +/- 1.2%. The difference between these two strains was statistically significant (P = 0.0297). Hyphae did not penetrate into the deep layers of the cornea in any of the six rabbits infected with VE175. The grading of clinical disease was consistent with histology, in that strain SC5314 caused more severe infection than VE175 and the difference was statistically significant (P = 0.0048). There was no difference in isolate recovery. CONCLUSIONS: Wild-type strains of C. albicans can differ significantly in virulence as measured by depth of fungal invasion into corneas and clinical evaluation of infection. Further characterization of the intrinsic genetic differences between such strains may help identify factors responsible for fungal virulence.

Contact lens-induced infection--a new model of Candida albicans keratitis.

PURPOSE: A model of experimental keratomycosis was established that mimics human disease in which the only fungi present are those that are actively growing within the cornea. METHODS: Dutch-belted rabbits received a subconjunctival injection of triamcinolone acetonide to one eye. One day later the epithelium was removed from the central cornea and a standardized inoculum of Candida albicans blastoconidia was placed on the corneal surface and covered with a contact lens. The lids were closed with a lateral tarsorrhaphy. After 24 hours, the lid sutures and contact lens were removed. Five days later the animals were killed, and their corneas were subjected to separate isolate recovery and histology studies. A group of similarly infected rabbits without corticosteroid injection served as controls. RESULTS: Both groups developed invasive corneal disease. Although isolate recovery was not significantly different from corticosteroid-treated rabbits compared with controls, fungal biomass was increased. Hyphal invasion was limited to the anterior cornea in control eyes, but penetrated deep stroma in most of the corticosteroid-treated rabbits. CONCLUSIONS: Invasive corneal disease can be established with a surface inoculum. Corticosteroid administration increased corneal penetration of hyphae. Quantitative isolate recovery is not a reliable measure of the fungal load within the cornea.

Half corneal light shield as a delivery system for standardized application of mitomycin C.

PURPOSE: The authors develop a simple and economical method of applying reproducible intraoperative doses of mitomycin C for glaucoma filtering surgery. METHODS: A three-part protocol was developed to study several properties of half corneal light shields (HCLSs). Part A tested the amount of mitomycin C (0.4 mg/ml) absorbed, the expansion dimensions attained, and the amount released to filter paper. In part B, the in vitro release of mitomycin C to an enucleated pig eye was examined. In part C, the in vivo release during intraoperative filtering surgery was tested. RESULTS: The amount of mitomycin C solution absorbed by the HCLSs ranged from 1.07 x 10(-2) mg to 1.19 x 10(-2) mg; expansion width ranged from 6.8 mm to 7.0 mm; expansion height ranged from 3.6 mm to 3.8 mm; expansion thickness was constant at 0.6 mm. The amount of solution released to filter paper ranged from 6.8 x 10(-3) mg to 8.6 x 10(-3) mg. The amount of solution transferred to the pig eye ranged from 1.0 x 10(-3) mg to 2.7 x 10(-3) mg. The amount of solution released in filtering surgery ranged from 2.0 x 10(-3) mg to 4.8 x 10(-3) mg. CONCLUSIONS: The contact surface area, the amount absorbed, and the amount released by each HCLS was reproducible. The uniform thickness theoretically provides a uniform distribution of mitomycin C. This method may allow standardization of intraoperative mitomycin C application, and may reduce the incidence of complications.

Induction of rabbit cyclooxygenase 2 in the anterior uvea following glaucoma filtration surgery.

PURPOSE: This study was undertaken to evaluate for the presence of cyclooxygenase 2 (COX2) gene expression in the anterior uvea of rabbits following glaucoma filtration surgery. METHODS: One of the following surgical procedures were performed on the right eye of New Zealand white albino rabbits: (1) paracentesis (2.5 mm limbal incision); (2) iridectomy through a 2.5 mm limbal incision; (3) lamellar scleral flap formation or (4) full glaucoma filtration surgery. The animals were sacrificed within 3 hours of post-surgery, and the anterior uveal tissues were isolated. Polymerase chain reaction-based techniques were employed to assay for the presence of COX2 transcript. RESULTS: A partial coding sequence of the previously unreported rabbit COX2 gene was obtained. COX2 mRNA was detected in the operated eyes of animals that underwent either full filtration surgery or iridectomy through a limbal incision. CONCLUSIONS: In normal rabbit anterior uveal tissue, there appears to be minimal expression of COX2 message. After experimental glaucoma filtration surgery, there is rapid induction of COX2 message.

Development of a chitin assay for the quantification of fungus.

Chitin, a unique structural polysaccharide found in fungi and arthropods, is not produced by vertebrates. Thus, the potential applications of a specific and sensitive assay for chitin are numerous, including the evaluation of the extent of fungal keratitis. Chitin is a homopolymer of beta (1, 4) linked D-N-acetylglucosamine. We have developed a simple and reproducible assay for chitin and applied it to Candida albicans cultures. The assay involves homogenization of the culture and treatment with 21.1 M KOH to remove soluble materials, including proteins. This base treatment also deacetylates the chitin to the glucosamine polymer, chitosan. Chitosan is hydrolyzed by 0.5 M H2SO4 to glucosamine monomers which are then deaminated by the addition of NaNO2 to the acid solution. The resulting 2,5-anhydromannose is reduced by NaB[3H]4 to 1-[3H] 2,5-anhydromannitol. This radiolabelled sugar is isolated by paper chromatography and quantified via liquid scintillation. The sensitivity of this assay is assessed by comparison of colony forming units (CFU's) with a glucosamine standard. A typical run of the assay detects 53.1 CFU/c.p.m., and 356,000 c.p.m. per nanomole of N-acetylglucosamine. The specificity of the assay is very high because of the unique nature of chitin. This method of chitin determination may be a useful alternative method for future investigations involving the study of fungal infections in mammalian tissues.

Socioeconomics viewpoint: the need for an update of the clinical practice guideline on cataract.

In June 1994, the Agency for Health Care Policy and Research (AHCPR), Washington, DC, called a meeting to hear opinions on the need for a reconstituted panel to revise the recently published clinical practice guideline Cataract in Adults: Management of Functional Impairment. The need and timing of a revision depend essentially on the answer to two questions: (1) Are there serious flaws in the previous panel's work that would necessitate a re-review? or (2) Is there new scientific information that can be critically assessed that would substantially alter the recommendations of the guideline? It is important to consider these questions with care because any revision is likely to be both costly and time-consuming.

The relationship of corneal epithelial defect size to drug penetration.

OBJECTIVE: To determine the relationship between corneal epithelial defect size and corneal penetration of a triazole antifungal drug in an animal model. METHODS: Corneas of adult rabbits were débrided of epithelium 25%, 50%, 75%, or 100% of surface area; the untreated fellow eye served as a control. Tritiated saperconazole was applied to each cornea every 5 minutes for 1 hour. The animals were killed and the cornea and aqueous of each eye were assayed for radiolabel activity. RESULTS: Removal of 25% of the corneal epithelium produced an increase in corneal saperconazole concentration compared with eyes with intact epithelium. Increasing epithelial defect size from 25% to 50% produced a ninefold increase in mean corneal drug concentration (P = .0001). There was no further increase in corneal drug levels in eyes with 75% or 100% epithelial defects. A similar threshold effect was observed in aqueous drug concentration between 25% and 50% débridement (P = .0001). CONCLUSION: In this experimental model, an apparent threshold was noted between 25% and 50% epithelial defect area, beyond which larger defects did not significantly increase drug penetration into the cornea or aqueous. This may be of clinical benefit in circumstances in which epithelial débridement is considered to enhance drug penetration.

Cyclodialysis cleft following a scleral tunnel incision.

We report a case of ocular hypotony secondary to a cyclodialysis cleft that developed following a phacoemulsification procedure in which a scleral tunnel incision was used. A cyclodialysis cleft should be suspected in cases of persistent postoperative hypotony.

Restoration of intraocular pressure after streptococcus endophthalmitis with vitrectomy.

A bleb infection and subsequent endophthalmitis developed in the left eye of a 68-year-old man who had had a trabeculectomy. Vitreous injections of vancomycin and gentamicin were given, and vitreous cultures grew alpha-Streptococcus. Postoperatively, as the intraocular inflammation resolved, intraocular pressure (IOP) markedly decreased secondary, in our judgment, to ciliary body ischemia. A pars plana vitrectomy relieved the tractional bands and restored the IOP.

Ocular pharmacokinetics of orally administered azithromycin in rabbits.

Azithromycin was orally administered to Dutch-belted rabbits following extracapsular lens extraction in one eye. At various times the animals were sacrificed, and serum and ocular tissues were obtained for drug level determination by HPLC-EC. Following a single dose, peak levels of drug in ocular tissues were measured within 8 hours (cornea > 0.5 micrograms/g [15mg/kg]; > 1.5 micrograms/g [3Omg/kg]). Highest levels were obtained in iris and ciliary body ( > 15 micrograms). Measurable tissue levels persisted for at least 120 hours. Trough levels increased proportionately during drug multiple dose administration. Five days following five daily 15mg/kg doses, corneal levels exceeded 0.5 micrograms/g, and iris and ciliary levels were higher than 15 micrograms/g. Aqueous humor and serum levels were equivalent. Vitreous humor levels, though higher than aqueous humor, were consistently < 1 microgram/ml. Extracapsular cataract extraction did not significantly affect drug uptake.

The qualitative evaluation of the pharmacokinetics of subconjunctivally injected antifungal agents in rabbits.

Dutch-belted rabbits with corneal epithelium either intact or debrided were injected subconjunctivally with 300 microliters of one of six antifungal agents: 10 mg/ml miconazole, 5 mg/ml fluconazole, 5 mg/ml ketoconazole, 2.5 mg/ml itraconazole, and 5 mg/ml amphotericin B. At intervals of 10 min to 96 h after injection, animals were killed and corneas removed at the limbus. Three vertical strips from the right cornea and four contiguous 3-mm disks trephined from the central vertical axis of the left cornea were placed on agar plates seeded with an appropriate indicator organism. After 24 h of incubation, the zones of inhibition were measured. For itraconazole, miconazole, fluconazole, saperconazole, and ketoconazole, central corneal levels peaked by 2 h in normal and debrided corneas. Little or no drug was detectable after 4-8 h, except for itraconazole, which persisted in the cornea for at least 24 h in both normal and debrided corneas. Peak levels of amphotericin B in the central cornea were achieved after 2 h in rabbits with debrided corneas, with no drug activity measured after 8 h. There were no detectable levels of drug found in the central corneas of rabbits with intact corneal epithelium. On the basis of this pilot study, the method offers a rapid approach to the screening of antifungal agents for possible use by subconjunctival injection.