EyeNet Magazine

Journal Highlights

New Findings from Ophthalmology, AJO and Archives

November’s Ophthalmology:
• Promising Wound Barrier: 2-Octyl Cyanoacrylate in Cataract Surgery
• Trimethoprim/Sulfamethoxazole Compares to Classic Therapy for Toxoplasmosis
• Intravitreal Triamcinolone Potent for Uveitic Cystoid Macular Edema
• Thrombophilic Gene Polymorphisms Not Major Factors for Branch Retinal Vein Occlusion
• Permanent Visual Loss Not Common With Proliferative Sickle Cell Retinopathy

October's American Journal of Ophthalmology:
• Vitrase for the Management of Vitreous Hemorrhage
• Persistence and Adherence in Glaucoma Therapy
• Cost-Utility of PDT in Eyes With Neovascular Macular Degeneration
• Risk Factors for Corneal Transplantation in Patients With Keratoconus

September's Archives
• Genetic Risk of Rhegmatogenous Retinal Detachment
• Some Baseline Optic Disc Measurements Associated With Primary Open-Angle Glaucoma

Roundup of Other Journals:
• Upregulation of the A3 Adenosine Receptor in Pseudoexfoliation Syndrome
• Intralesional Immunotherapy for Warts
• National Health Vision Objectives Faltering


Promising Wound Barrier: 2-Octyl Cyanoacrylate in Cataract Surgery
November's issue

In light of reports questioning the stability of sutureless clear corneal wounds in cataract surgery, Meskin et al. investigated whether 2-octyl cyanoacrylate with parabens (Liquid Bandage) would effectively serve as an adjunct wound sealant and barrier against the inflow of ocular surface fluid after this procedure.

In this small prospective pilot research study, 51 eyes of 51 patients underwent a 2.75-millimeter clear corneal, triplanar, temporal incision, followed by routine phacoemulsification. At the conclusion of each case, a modified microsponge with one to two drops of 2-octyl cyanoacrylate with parabens was applied in a smooth layer to the wound. All 51 eyes demonstrated intraoperative watertight wound closure after application of the material. Forty-five eyes had tissue adhesive still completely covering the wound on postoperative day 1.

The authors conclude that 2-octyl cyanoacrylate with parabens shows potential as a temporary barrier and sealant for clear corneal wounds and called for further investigation of this compound to establish evidence-based practice guidelines.

Trimethoprim/Sulfamethoxazole Compares to Classic Therapy for Toxoplasmosis
November’s issue

When comparing the standard therapy for ocular toxoplasmosis, pyrimethamine and sulfadiazine, to trimethoprim/sulfamethoxazole (TMP/SMX), Soheilian et al. found similar efficacy in reduction in retinal lesion size and improvement in visual acuity.

The authors conducted a prospective, single-blind clinical trial of 59 patients with active ocular toxoplasmosis who were randomly assigned to one of the two therapies. Mean reductions in size of retinal lesions were 61 percent in the classic therapy group and 59 percent in the TMP/SMX group. In addition, no significant difference was found in visual acuity between the two groups. The overall recurrence rate after 24 months’ follow-up was about 10 percent in each group.

The authors conclude that TMP/SMX is a viable alternative to classic treatment, with greater availability, lower cost and a safer drug profile in immune-competent patients with two functional eyes and with lesions not in immediate proximity to the macula.

Intravitreal Triamcinolone Potent for Uveitic Cystoid Macular Edema
November’s issue

A retrospective noncomparative case series studying intravitreal triamcinolone acetate (TA) in the treatment of uveitic cystoid macular edema (CME) indicates that intravitreal TA is a potent therapy for this condition.

The study by Kok et al. involved 65 eyes of 54 patients with uveitis-related CME who had not adequately responded to treatment combinations of oral corticosteroids, periocular orbital floor corticosteroid injections and second-line immunosuppressive agents.

Each eye received an intravitreal injection of 4 milligrams/0.1 milliliter of TA. Eyes with the most visual improvement had had CME for less than a year. Eyes of younger patients also attained better vision after treatment. In 43.1 percent of eyes, treatment was associated with a rise in IOP, a transient and treatable side effect. The authors warn that results of this study should be interpreted with caution given its nonrandomized and uncontrolled design. Nevertheless, intravitreal TA shows potential in treating uveitic CME, especially in younger patients and those with CME for less than 12 months.

Thrombophilic Gene Polymorphisms Not Major Factors for Branch Retinal Vein Occlusion
November’s issue

Are thrombophilic gene polymorphisms major risk factors for BRVO? According to data from a retrospective case-control study by Weger et al., the answer is no. The researchers conducted the study in response to earlier hypotheses indicating that gene polymorphisms affecting hemostasis may play a role in the pathogenesis of BRVO.

Six gene polymorphisms affecting hemostasis were investigated in a cohort of 294 patients with BRVO and 294 controls matched for age and gender. Genotype distributions of the six gene polymorphisms did not differ significantly between the patients and control subjects. However, the prevalence of arterial hypertension and hypercholesterolemia was significantly increased among patients with BRVO.

Taking into consideration the general limitations of a retrospective study, the authors conclude that routine screening for polymorphisms should not be recommended for these patients given the data suggesting that none of the investigated gene polymorphisms was a major risk factor for BRVO.

Permanent Visual Loss Not Common With Proliferative Sickle Cell Retinopathy

November’s issue

The Jamaican Cohort Study of Sickle Cell disease has yielded longitudinal data for more than two decades. The study has followed 307 sickle cell (SS) patients and 166 SS-hemoglobin C (SC) disease patients born between 1973 and 1981 and living in Jamaica. Downes et al. used information from the study to explore the incidence, prevalence and natural history of proliferative sickle cell retinopathy (PSR).

As of January 2000, PSR had developed in 59 patients. The prevalence was greater in patients with SC disease; by the ages of 24 to 26 years, PSR had occurred in 43 percent of patients with SC disease and in 14 percent of patients with SS disease.

While the data confirmed a greater incidence and severity of PSR in patients with SC disease, permanent visual loss was not common in individuals observed up to age 26. This discrepancy between the incidence of PSR and that of visual loss makes it difficult to answer the question of whether routine screening and prophylactic treatment are justified.


Vitrase for the Management of Vitreous Hemorrhage
American Journal of Ophthalmology
October’s issue

There is no simple therapy for vitreous hemorrhage. Kuppermann et al. from the Vitrase for Vitreous Hemorrhage Study Group evaluated the efficacy of intravitreal ovine hyaluronidase for the management of vitreous hemorrhage in two prospective, randomized, placebo-controlled, double-masked studies.

Eligible patients with severe vitreous hemorrhage > 1 month duration with BCVA worse than 20/200 were randomized to 55 or 75 international units of ovine hyaluronidase, or a control saline solution.

Primary efficacy was defined as clearance of hemorrhage sufficient to see the underlying pathology and the completion of treatment when indicated, and was measured at months 1, 2 and 3. Key secondary endpoints were: > 3-line improvement in BCVA, hemorrhage density reduction and therapeutic utility assessment. The intent-to-treat population consisted of 1,125 patients. At baseline, 76.3 percent of these had diabetes, 90.4 percent were not able to read any letters on the eye chart, and mean hemorrhage duration was 120 days.

By months 1, 2 and 3 post-treatment, primary efficacy had been reached by 13.2, 25.5 and 32.9 percent of patients in the 55 IU group, compared with 10.6, 21.2 and 30.5 percent from the same months in the 75 IU group, and 5.5, 16.2 and 25.6 percent of saline-treated patients. Key secondary endpoints confirmed the treatment effect at both doses and all time points (P < 0.01).

The results suggest a significant therapeutic utility of ovine hyaluronidase in the management of vitreous hemorrhage, with a dose of 55 IU demonstrating increased efficacy over 75 IU or saline.

Persistence and Adherence in Glaucoma Therapy
American Journal of Ophthalmology
October’s issue

Compliance with glaucoma therapy has always been a challenge for patients and their physicians. Friedman et al. described the patterns and predictors of adherence (compliance) to and persistence with treatment among patients who are diagnosed either with glaucoma or as glaucoma suspects in a retrospective study using insurance claims data.

Data on newly treated individuals with diagnosed glaucoma (n = 3,623) and suspect glaucoma (n = 1,677) were obtained from health care claims in the Ingenix Research Database. For each of these groups, the authors calculated the duration of continuous treatment with the initially prescribed medication (persistence) and the prevalence of use of the initial medication at various time points (adherence). Four drug classes were included: beta blockers, alpha agonists, carbonic anhydrase inhibitors and prostaglandin analogs.

Nearly one-half of those individuals who had filled a glaucoma prescription discontinued all topical ocular hypotensive therapy within six months, and just 37 percent of these individuals recently had refilled their initial medication at three years after the first dispensing.

Persistence and adherence were substantially better with prostaglandins than with other drug classes, and patients with diagnosed open-angle glaucoma were more likely to adhere to treatment than those with suspected glaucoma.

Cost-Utility of PDT in Eyes With Neovascular Macular Degeneration
American Journal of Ophthalmology
October’s issue

Brown et al. assessed the value conferred by photodynamic therapy and the cost-utility of PDT for the treatment of classic, subfoveal choroidal neovascularization associated with age-related macular degeneration. They evaluated average cost-utility using clinical trial data, patient-based time trade-off utility preferences and a third party insurer cost perspective.

Five-year visual acuity data from the TAP (Treatment of Age-related Macular Degeneration With Photodynamic Therapy) Investigation were modeled into a 12-year, value-based, reference case, cost-utility model utilizing year 2004 Medicare costs and an outcome of $/QALY (dollars/quality-adjusted life-year). Discounting of outcomes and costs using net present value analysis with a 3 percent annual rate was performed as recommended by the Panel for Cost-Effectiveness in Health and Medicine.

PDT with verteporfin (Visudyne) for classic subfoveal CNV confers an 8.1 percent quality of life (value) improvement over the 12-year life expectancy of the reference case, while during the last eight years the value improvement is 9.5 percent. The average cost-utility of the intervention is $31,103/QALY. Extensive one-way sensitivity analysis values range from $20,736/QALY if treatment efficacy is increased by 50 percent to $62,207 if efficacy is decreased by 50 percent, indicating robustness of the model.

PDT using verteporfin to treat classic subfoveal CNV is a very cost-effective treatment by conventional standards. The marked improvement in cost-effectiveness compared with a previous report can be explained by the fact that the treatment benefit increasingly accrues during five years of follow-up while the number of yearly treatments diminishes markedly during that time.

Risk Factors for Corneal Transplantation in Patients With Keratoconus
American Journal of Ophthalmology
October’s issue

Reeves et al. sought to determine the clinical and demographic risk factors for corneal transplantation in keratoconus patients in a case control study at the Duke University Eye Center. Cases were defined as eyes undergoing transplantation, and controls were defined as eyes that did not. The two groups were compared to determine clinical and demographic risk factors for corneal transplantation.

A total of 131 eyes with keratoconus were studied, with 59 cases compared with 72 controls. The groups were similar with respect to sex and race. Significant univariate risk factors for corneal transplantation were best-corrected vision worse than 20/40, cylinder > 10 D and average keratometry > 55 D.

In multivariate analysis, age 30 or younger conferred a sevenfold increased risk of transplantation compared with ages of more than 40. Multivariate analysis showed duration of disease five years or less and steep average keratometry as additional risk factors.

A subset of young keratoconic patients with high keratometry values may represent an underrecognized risk group for corneal transplantation. BCVA worse than 20/40 at presentation and astigmatism are other clinical indicators of increased risk of corneal transplantation in these patients.

Genetic Risk of Rhegmatogenous Retinal Detachment
Archives of Ophthalmology

Sioe et al. assessed the genetic risk of nonsyndromic rhegmatogenous retinal detachment (RRD) in a familial aggregation. The study included 181 patients with RRD and 408 controls without RRD.

The probands generated 1,090 and 2,345 relatives, respectively, for analysis. Thirteen (1.2 percent) familial RRDs were diagnosed in 10 case probands, and nine (0.4 percent) RRDs in eight control probands. Siblings and offspring of cases had a higher incidence of RRD independent of age, sex and myopia.

The cumulative lifetime risk of RRD was 7.7 percent for relatives of cases and 3 percent for relatives of controls, yielding a risk ratio of 2.6 (95 percent CI 1.1–6.2).

In summary, these data show that familial occurrence of RRD is a risk factor for RRD. Genetic factors apart from myopia may explain the increased familial risk.

Some Baseline Optic Disc Measurements Associated With Primary Open-Angle Glaucoma
Archives of Ophthalmology

Zangwill et al. evaluated 865 eyes from 438 participants with good quality baseline images in the Confocal Scanning Laser Ophthalmoscopy (CSLO) Ancillary Study Group of the Ocular Hypertension Treatment Study (OHTS).

Forty-one eyes from 36 participants developed POAG during the follow-up period. Several baseline topographic optic disc measurements alone or when combined with clinical and demographic factors were significantly associated with the development of POAG, including larger cup-to-disc ratio, mean cup depth, mean height contour, cup volume and reference plane height, and smaller rim area, rim area to disc area, and rim volume.

In addition, classification as “outside normal limits” by the Heidelberg Retina Tomograph and the Moorfields Regression Analysis (overall, global, temporal inferior, nasal inferior and superior temporal regions) was significantly associated with the development of POAG.

Ophthalmology summaries are written by Lori Baker Schena and edited by John Kerrison, MD. American Journal of Ophthalmology summaries are edited by Thomas J. Liesegang, MD. Archives of Ophthalmology summaries are written by the lead authors.

Roundup of Other Journals

Upregulation of the A3 Adenosine Receptor in Pseudoexfoliation Syndrome
Journal of Investigative Ophthalmology and Visual Science

The purine nucleoside adenosine functions as a modulator of a variety of physiological processes including aqueous humor secretion and IOP. It does this via activation of four pharmacologically and biochemically distinct adenosine receptors: A1, A2A, A2B and A3.

Schlötzer-Schrehardt et al. examined the role of the adenosine system in the pathophysiology of pseudoexfoliation (PEX) syndrome, which is typically associated with anterior chamber hypoxia and elevated IOP. They consistently found a selective, approximately tenfold upregulation of A3 receptor mRNA and protein in the nonpigmented ciliary epithelium of all PEX eyes, with and without glaucoma, compared with the normal and glaucomatous control eyes. This was induced by both hypoxia and oxidative stress in vitro, together with increased levels of inosine, hypoxanthine and xanthine in the supernatants.

The authors conclude that the reduction of chloride channel activity with A3 receptor antagonists may lead to an alternative approach for treating ocular hypertension in patients with PEX who are refractory to standard medical therapy.

Intralesional Immunotherapy for Warts
Archives of Dermatology

Warts account for 8 percent of dermatology visits, and primary treatments often involve topical salicylic acid, cryotherapy with liquid nitrogen, excision, laser vaporization and bleomycin sulfate injection.

Horn et al. have taken a different therapeutic approach, expanding on earlier research demonstrating that intralesional immunotherapy with mumps, Candida or Trichophyton skin test antigens was efficacious in treating warts.

In this study, the investigators randomized 233 patients with one or more common warts to injection of antigen alone, antigen plus interferon alpha2b, interferon alpha2b alone or normal saline.

Patients in all treatment arms responded, but those who received antigen were significantly more likely to respond.

Interferon did not enhance the response rate and did not differ from normal saline.

The authors repeatedly observed that untreated warts resolved after injection of only one wart, prompting them to speculate that intralesional immunotherapy induced human papillomavirus-directed immunity. They conclude that intralesional immunotherapy for common warts is effective and safe, and may be particularly useful in patients with numerous warts covering large areas.

National Health Vision Objectives Faltering
Morbidity and Mortality Weekly Report

The national health objectives for 2010, established by the U.S. Department of Health and Human Services, include three vision objectives for children: 1) reducing visual impairment and blindness, 2) increasing the proportion of preschool children who receive vision screening and 3) increasing the use of protective eyewear in recreational activities and hazardous situations around the home.

To provide baseline data for these objectives, the Centers for Disease Control and Prevention analyzed data from the 2002 National Health Interview Survey (NHIS).
This report indicates that the national health objective for 2010 to reduce the number of children with visual impairment and blindness to 20 per 1,000 children has not yet been achieved: in 2002, the prevalence was 25 per 1,000 children, nearly the same as for the baseline year of 1997.

In addition, the percentage of children under age six who had received a vision test, 36.3 percent, was below the national health objective target of 52 percent.

Finally, in 2002, about 50 percent of children were involved in sports, yet less than 15 percent of those used protective eyewear; 20 percent is the 2010 goal. The report concludes that NHIS data should continued to be used to create and implement strategies to improve the nation’s visual health.

Roundup is written by Lori Baker Schena and edited by Deepak P. Edward, MD.


Editor’s Kind of Town

The demands of a busy ophthalmology practice do not always leave the clinician time to nurture her or his intellectual curiosity and stay current with the peer-reviewed literature. Consequently, the editors of the American Journal of Ophthalmology, Archives of Ophthalmology and Ophthalmology would like to invite this year’s Annual Meeting attendees to a review of recently published papers that have demonstrated relevance to the profession.

Join them in Chicago on
Sunday, Oct, 16, for
The Editors’ Choices Symposium

This event will take place from 3:45 to 5:15 p.m. in North Hall B of McCormick Place. There is no charge for attending the symposium.

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