Robert D. Fechtner

Mechanisms of optic nerve damage in primary open angle glaucoma.

Several mechanisms have been postulated to explain the optic nerve damage that occurs in primary open angle glaucoma (POAG). No single mechanism can adequately explain the great variations in susceptibility to damage and the patterns of damage seen in this syndrome. The etiology of POAG is likely to be multifactorial. Mechanical, vascular and other factors may influence individual susceptibility to optic nerve damage. An enhanced understanding of the nature of the optic nerve damage in POAG and improved methods of study may result in earlier diagnosis or may allow us to distinguish among different pathological processes all currently grouped under the diagnosis of POAG. As we gain a better understanding of the neuropharmacology and cellular biology of injury and repair of the visual system we will undoubtedly refine the concepts of glaucomatous optic neuropathy.

Antifibrotics and Wound Healing in Glaucoma Surgery

When medical and laser therapy fail to control intraocular pressure, glaucoma filtration surgery needs to be performed. Glaucoma surgery is unique in that its success is linked to interruption of the wound-healing response in order to maintain patency of the new filtration pathway. In this article we will review the wound-healing pathway and the pharmacologic interventions that have been employed clinically and experimentally to interrupt wound healing, particularly steroids and the antifibrotic agents 5-fluorouracil and mitomycin C. A review of the published literature looking at use of these agents to enhance success as well as the associated complications are presented, critiqued, and interpreted in order to put the studies in proper perspective. Future directions and recommendations regarding use of these agents are available and an introduction to newer wound modulating agents such as anti-transforming growth factor beta 2 is presented.

Anterior uveitis associated with latanoprost

PURPOSE To report the association of anterior uveitis with the use of latanoprost. METHODS We studied four patients with complicated open-angle glaucoma who had anterior uveitis associated with the use of latanoprost. The uveitis was unilateral and occurred only in the eye receiving latanoprost in three patients. In one patient, latanoprost was used in both eyes, and the uveitis was bilateral. Four of five eyes had a history of prior inflammation and/or prior incisional surgery. All patients were rechallenged with the drug. RESULTS The uveitis improved after cessation of latanoprost with or without topical corticosteroids. It recurred after rechallenging with latanoprost in all eyes. CONCLUSION There is a possible association between latanoprost and anterior uveitis. Topical prostaglandin analogs may be relatively contraindicated in patients with a history of uveitis or prior ocular surgery. This association may also be possible in eyes that have not had previous uveitis or incisional surgery.

Prevalence of ocular surface complaints in patients with glaucoma using topical intraocular pressure-lowering medications.

Purpose: To determine the prevalence of ocular surface disease (OSD) in patients with glaucoma using topical intraocular pressure (IOP)-lowering therapy. Methods: This prospective observational study enrolled patients with primary open-angle glaucoma or ocular hypertension who were on a topical IOP-lowering medication regimen. Enrolled patients completed the ocular surface disease index (OSDI) and OSDI scores (0-100, with 0 representing no symptoms) were calculated for each patient. Medical history, demographics, and concomitant medication information were also collected. Results: Overall, 630 patients from 10 sites participated. Of these, 305 patients (48.4%) had an OSDI score indicating either mild (n = 134, 21.3%), moderate (n = 84, 13.3%), or severe (n = 87, 13.8%) OSD symptoms. OSDI scores were significantly different between patients with and without a prior diagnosis of dry eye syndrome (25.2 ± 15.4 vs 15.4 ± 15.8, respectively; P = 0.0036) and between patients who did and did not use artificial tears at the time of study participation (23.0 ± 15.6 vs 15.3 ± 15.8, respectively; P = 0.0046). Mean OSDI scores varied significantly with the number of topical IOP-lowering medications used, with higher (more severe) OSDI scores in patients using multiple IOP-lowering medications. Specifically, patients on a single medication had a mean OSDI score of 12.9 ± 13.1, which was significantly lower than those of patients on 2 (16.7 ± 17.0; P = 0.007) or 3 medications (19.4 ± 18.1; P = 0.0001). Conclusions: OSD is prevalent among medically treated patients with glaucoma. The severity of OSD symptoms is positively correlated to the number of IOP-lowering medications used.

Fixed combinations of topical glaucoma medications.

Purpose of review Topical medical therapy remains the first line of treatment in the management of glaucoma. Utilization studies and clinical trials have demonstrated that many patients with glaucoma require multiple medications to achieve adequate control of intraocular pressure. Fixed combinations of commonly used drugs have been developed, tested, and in some (but not all) cases, approved for use in the United States and abroad. In this review the authors discuss the principles of fixed combination therapy and examine the existing fixed combinations. Recent findings The first modern combination product was the dorzolamide–timolol fixed combination. It works better than either constituent and at least as well as concomitant therapy with both constituents. In comparison with newer agents, the dorzolamide–timolol fixed combination was equal in efficacy to latanoprost monotherapy, timolol and unoprostone concomitant therapy, and timolol and brimonidine concomitant therapy. Concomitant latanoprost and brimonidine demonstrated better efficacy than the dorzolamide–timolol fixed combination. The latanoprost–timolol fixed combination is available in many countries but not the United States. This combination has demonstrated modest additional efficacy over latanoprost monotherapy. The latanoprost–timolol fixed combination provided greater efficacy than concomitant timolol and brimonidine. Summary Fixed combinations offer benefits of convenience, cost, and safety, but limit individualization of dosing. Understanding the advantages and disadvantages of prescribing fixed combinations facilitates success in using these products in clinical practice.

Automated perimetry: A report by the American academy of ophthalmology

OBJECTIVE The purpose of this document is to summarize and evaluate the effectiveness of new automated perimetry tests and algorithms in diagnosing glaucoma and detecting disease progression. METHODS A literature search on automated perimetry retrieved over 300 citations from 1994 to 2001, of which 71 were selected as relevant to this assessment. The quality of the evidence obtained from these studies was assessed by the methodologist. RESULTS The four automated perimetry techniques described in this assessment are short wavelength automated perimetry (SWAP), frequency doubling technology perimetry (FDT), high-pass resolution perimetry (HPRP), and motion automated perimetry (MAP). The algorithms described are Swedish interactive threshold algorithm (SITA) and SITA fast. With the exception of SWAP, these techniques and algorithms reduce testing time and inconsistent patient performance when compared with conventional full threshold testing. CONCLUSIONS Short wavelength automated perimetry detected visual field loss earlier than standard threshold automated perimetry, with a sensitivity and specificity of about 88% and 92% respectively. However, it is a lengthy, demanding test, is sensitive to media opacities, and has a greater magnitude of long-term fluctuation compared with standard threshold automated perimetry, which make it difficult to assess disease progression accurately. When compared to standard threshold automated perimetry, FDT perimetry showed sensitivity and specificity greater than 97% for detecting moderate and advanced glaucoma, and sensitivity of 85% and specificity of 90% for early glaucoma. As FDT perimetry has a short testing time and is resistant to blur and pupil size, it may be a useful screening tool. In a longitudinal study, high-pass resolution perimetry was more effective than standard threshold automated perimetry in monitoring progressive glaucomatous loss, detecting progression at a median of 12 months earlier in 54% of patients studied. Motion automated perimetry demonstrated usefulness in detecting early glaucomatous visual loss in a longitudinal study. Studies on SITA demonstrated greater sensitivity and reproducibility and less intertest variability when compared to standard full threshold testing and a 50% reduction in testing times. A study comparing standard full threshold, SITA, and SITA fast found a sensitivity of 95% for the first two techniques and 93% for SITA fast. Long-term follow-up studies are needed to assess the ability of these techniques to detect progression of glaucoma over time.

Complications in resident-performed phacoemulsification cataract surgery at New Jersey Medical School

Aim: To describe the complications related to cataract surgery performed by phacoemulsification technique by third-year ophthalmology residents at New Jersey Medical School, who are trained to perform phacoemulsification without any prior experience with extracapsular extraction. Design: Retrospective, observational case series. Methods: A retrospective chart review of 755 patients who underwent cataract surgery by third-year residents between July 2000 and June 2005 at the Institute of Ophthalmology and Visual Science was performed. Details of intraoperative complications (posterior capsular rupture, vitreous loss, subluxation of lens fragments into the vitreous, extracapsular cases converted to phacoemulsification, retinal detachment, vitreous haemorrhage and haemorrhagic choroidals) of the cases done by phacoemulsification technique were recorded. Results were analysed and compared with complication rates reported from other residency programmes and from experienced ophthalmologists. Results: Of 755 cataract surgeries, 719 were performed using phacoemulsification technique. Posterior capsule disruption occurred in 48 (6.7%), vitreous loss in 39 (5.4%) and dislocated lenticular fragments in 7 (1.0%) of 719 cases that underwent phacoemulsification technique. Subsequent pars plana lensectomy was required in 5 (0.7%) cases; 1 case (0.1%) experienced retinal detachment and haemorrhagic choroidal detachment. Conclusion: The residents can perform phacoemulsification well with a very low complication rate, without prior training with extracapsular cataract extraction technique.

Use of Fixed-Dose Combination Drugs for the Treatment of Glaucoma

Glaucoma is a leading cause of irreversible visual loss. This potentially blinding disease is a progressive optic neuropathy associated with elevated intraocular pressure (IOP). Initial therapy for glaucoma typically consists of topical medications or laser treatment to lower IOP. Frequently, more than one medication is required to achieve adequate control of IOP. However, more medications means more bottles and greater complexity for the patient. There are several potential benefits of fixed combination medications compared with using the individual components separately. These include a reduction in the total number of drops and preservative instilled per day, cost savings, improved tolerability and compliance and avoiding the washout effect resulting from rapid-sequence instillation of multiple drops. Attempts to develop effective fixed combinations of glaucoma medications date back several decades. In recent years, fixed combinations of commonly paired drugs have been approved by various regulatory bodies in different countries and have gained wide acceptance. Current commercially available, fixed combination drugs include the topical β-adrenoceptor antagonist timolol 0.5% combined with a prostaglandin, a topical carbonic anhydrase inhibitor or an α-adrenoceptor agonist. Although there is no uniformity among registration trial designs, most published literature compares the efficacy of the fixed combination to the individual components and to concomitant use of both components. Various factors inherent to study design such as medication run-in, washout periods and peak and trough effects have to be taken into consideration when analysing the demonstrated efficacy of fixed combinations. Fixed combination treatments offer effective IOP control while reducing the washout effect and exposure to preservatives. They are also convenient. However, fixed combinations also remove the possibility of titrating the individual components both in terms of concentration and timing of administration. In addition, fixed combinations might not always provide the same efficacy as proper use of the individual components. The clinician must make individualised assessments when weighing the convenience of these medications against their limitations for specific patients.

Diffuse and localized nerve fiber layer loss measured with a scanning laser polarimeter: sensitivity and specificity of detecting glaucoma.

Purpose: To differentiate normal from diseased retinal nerve fiber layers (NFL) using a new method of analyzing polarimetry data that specifically targets patterns of diffuse and localized NFL loss. Methods: The NFL from a sample of 34 patients with primary open‐angle glaucoma (POAG), 34 patients with ocular hypertension, and 34 normal subjects were imaged using a scanning laser polarimeter (GDx; Laser Diagnostic Technologies, Inc., San Diego, CA). Diffuse loss was defined as a reduction in the peak‐to‐trough amplitude of the double‐hump NFL pattern, and localized loss was defined as a lowering of the correlation of thickness values between local regions shown previously to correspond in normal subjects. Results: Significant differences were found between the groups of normal subjects, patients with hypertension, and patients for both the amplitude and the correlational measures. The sensitivity and specificity calculated using optimal criterion values were 94% and 91%, respectively. Conclusions: These results suggest that NFL analysis targeting specific patterns of loss may be beneficial for differentiating normal NFL patterns from diseased NFL patterns, as well as for identifying patients at high risk.

Long-term incidence and timing of intraocular hypertension after intravitreal triamcinolone acetonide injection.

PURPOSE To describe the long-term incidence and timing of steroid-induced ocular hypertension after intravitreal triamcinolone acetonide (IVTA) therapy. DESIGN Retrospective case series of 929 eyes of 841 patients. PARTICIPANTS Patients with a variety of posterior segment disorders in a single group practice. INTERVENTION Pars plana injection of IVTA. MAIN OUTCOME MEASURES Intraocular pressure (IOP) and requirement for glaucoma surgery. RESULTS Overall, 929 eyes received >or=1 injections (mean, 1.6) of 4 mg of IVTA. During a mean follow-up period of 14+/-6.9 months, the Kaplan-Meier cumulative incidences of IOP elevations >21 mmHg at 6, 12, 18, and 24 months post-injection were 28.2%, 34.6%, 41.2%, and 44.6%, respectively; similarly, the incidences of eyes with IOP measurements >25 mmHg were 14.6%, 19.1%, 24.1%, and 28.2%, respectively. At the same time points, IOP-lowering medications were required by 13.0%, 16.9%, 20.7%, and 24.2% of eyes, respectively. Only 3 eyes (0.3%) required IOP-lowering surgery. Preexisting glaucoma, younger age, and a history of an IOP elevation after a previous IVTA injection were risk factors for IOP elevations after IVTA injection. The minimum and maximum follow-up were 3 weeks and 37 months. The mean rate of attrition in this study was 3% per month. CONCLUSIONS Elevations in IOP after IVTA injection are common. Younger patients and eyes with preexisting glaucoma or a history of a steroid response should be monitored more closely for IOP elevations after IVTA therapy.