EyeNet Magazine


 
Journal Highlights

New Findings from Ophthalmology, AJO and Archives
 
 

July’s Ophthalmology:

Cup-to-Disc Ratio Is Highly Heritable: IOP Is Moderately So

The Career Decisions of Graduating Residents

Most Effective IOP-Reducing Agents for Primary Open-Angle Glaucoma

Prevalence of Visual Impairment Is Low in Australian 6-Year-Olds

Fluocinolone Acetonide Implant Is Effective for Posterior Uveitis

American Journal of Ophthalmology:

Complications in Patients With Chronic Anterior Uveitis

Cataract Progression After Intravitreal Triamcinolone Injection

Predictive Factors for Progressive Optic Nerve Damage in Chronic Open-Angle Glaucoma

Evaluating the Accuracy of Diagnostic Tests in Glaucoma

Archives of Ophthalmology:

Acute Endophthalmitis Following Cataract Surgery

Cyclosporin vs. Tacrolimus for the Treatment of Uveitis

Need for Eye Care Among Seniors With Diabetes Mellitus in Fee-for-Service vs. Managed Medicare

Second Primary Cancers After Treatment of Choroidal Melanoma

Roundup of Other Journals:

Preventing Neurodegeneration in Inherited Glaucoma

Conjunctival Epithelial Involvement by Eyelid Sebaceous Carcinoma

A Potential Treatment for Tuberculosis

Topical Pimecrolimus and Tacrolimus in Atopic Dermatitis


Previews

Cup-to-Disc Ratio Is Highly Heritable: IOP Is Moderately So
Ophthalmology
July’s issue

Chang et al. have found that in an older, well-defined population, cup-to-disc ratio is highly heritable and IOP is moderately heritable. In addition, on average, siblings of glaucoma patients had higher IOPs and larger cup-to-disc ratios than siblings of nonglaucomatous probands.

For this research, the investigators recruited 726 siblings with a mean age of 74.7 years in 284 sibships from the population-based Salisbury Eye Evaluation Study. Salisbury is located on the eastern shore of Maryland.

They estimated the heritability of IOP to be 0.29 and cup-to-disc ratio to be 0.56. The authors noted that the IOP findings are in close agreement with the value of 0.36 recently reported for the Beaver Dam population.

These findings affirm heritable components of primary open-angle glaucoma responsible for increased IOP and cup-to-disc ratio. The authors plan future studies in order to identify genes responsible for these traits.

The Career Decisions of Graduating Residents
Ophthalmology
July’s issue

Which factors influence a graduating ophthalmology resident to pursue either subspecialty training or a comprehensive ophthalmology career?

To gain insight into this important decision, Gedde et al. sent out an anonymous survey to each graduating ophthalmology resident in February 2003. With a response rate of 50.8 percent, the survey showed that 64 percent of respondents  planned to pursue subspecialty training and 36 percent planned to practice comprehensive ophthalmology.

A multivariate analysis revealed that graduates who pursued subspecialty training did so to acquire special skills and because they perceived the subspecialties to have more prestige and a more favorable job market.

In contrast, those respondents planning a career in comprehensive ophthalmology cited anticipated work hours and geographic preference as major factors influencing their decision.

Additionally, those anticipating becoming comprehensive ophthalmologists planned to practice in a private group setting, while those seeking subspecialty training intended to practice in a university setting or were as yet undecided about practice preferences.

These data may prove helpful when shaping an appropriate physician workforce to meet future eye care needs in the United States.

Most Effective IOP-Reducing Agents for Primary Open-Angle Glaucoma
Ophthalmology
July’s issue

In the past decade, several new drugs have been introduced to lower IOP in glaucoma patients. To determine which were the most effective, van Der Valk et al. conducted a meta-analysis of 28 randomized clinical trials that reported 6,953 participants for the trough and 6,841 for the peak.

They found that all of the eight drugs that were evaluated lowered IOP more effectively than placebo. The highest reduction in IOP at peak was achieved by bimatoprost (33 percent), followed by latanoprost, travoprost, timolol,
brimonidine, betaxolol, dorzolamide, brinzolamide (17 percent) and placebo (5 percent).

The authors note that prostamide or prostaglandin analogs (along with the beta-blocker timolol) were most effective for lowering IOP by monotherapy in primary open-angle glaucoma or ocular hypertension. The beta-blocker betaxolol, alpha2-adrenergic agent brimonidine, carbonic anhydrase inhibitors, brinzolamide and dorzolamide were clearly less effective.

This study illustrates there are multiple options for effective monotherapy in POAG and ocular hypertension, enabling physicians to consider many different strategies for their patients.

Prevalence of Visual Impairment Is Low in Australian 6-Year-Olds
Ophthalmology
July’s issue

In a population-based, cross-sectional study of 1,736 6-year-old children, Robaei et al. report that refractive error (mostly uncorrected astigmatism) and amblyopia represent the most common causes of visual impairment in this population. The children were predominantly Caucasian and lived in Sydney, Australia.

The 1.4 percent myopia prevalence (myopia defined as spherical equivalent refraction < 0.5 D) in these school-aged children was among the lowest reported in the literature.  The finding was in contrast to the reported myopia prevalence in Taiwan and Singapore, which was as high as 20 percent in similar age groups. In addition, the low myopia rates among children in Australia were consistent with the prevalence of myopia in Australian adults, which also has been reported to be lower than among adults in Europe and the United States.

The reason for these regional differences remains unclear. The authors call for further investigation to gain insight regarding the etiology of refractive error.

Fluocinolone Acetonide Implant Is Effective for Posterior Uveitis
Ophthalmology
July’s issue

Long-term follow-up results from a pilot trial evaluating the use of a fluocinolone acetonide implant to treat posterior uveitis indicates that this approach can effectively control intraocular inflammation. However, the procedure is not without risks.

Jaffe et al. randomized 36 eyes of 32 patients with a history of recurrent noninfectious posterior uveitis to receive either a 0.59 milligrams or 2.1 mg fluocinolone acetonide intravitreal implant. Patients were followed for an average of nearly two years.

During this period, only five recurrences were recorded in the device-implanted eyes. In addition, visual acuity was stabilized or improved in most patients. The most common adverse event was a rise in IOP, which was managed by standard means. Four of the eight phakic eyes, each of which had some level of cataract at device implantation, subsequently underwent cataract extraction.

The authors conclude that the observed benefits of highly effective uveitic inflammatory control seem to outweigh the manageable risks. More research will help clarify this risk vs. benefit question.

Reviews

Complications in Patients With Chronic Anterior Uveitis
American Journal of Ophthalmology
2005;139:988-992

Menezo et al. identified the factors determining the ocular complications and visual outcome in patients with chronic anterior uveitis in a retrospective, noncomparative case study.

Ninety-one eyes of 68 patients with anterior uveitis that lasted longer than three months were divided into three groups: idiopathic chronic anterior uveitis, nonidiopathic chronic anterior uveitis and Fuchs’ uveitis. Visual acuity and complications such as posterior synechiae, cataract formation, raised IOP and posterior segment complications were evaluated. Poor visual outcome measured by life-table analysis was considered when logMAR (log of the reciprocal of Snellen visual acuity) visual acuity was 0.3 or worse.

No statistically significant differences in the visual outcome were found between the three groups of chronic anterior uveitis. Posterior synechiae formation was significantly increased in patients who had chronic anterior uveitis compared with those who had Fuchs’ uveitis. There was a trend among patients who had nonidiopathic chronic anterior uveitis to have an increased risk of cystoid macular edema compared with those who had idiopathic disease. There were no significant differences in visual outcome between any of the groups over time.

In this study, the visual prognosis for patients with chronic anterior uveitis generally seems good. Posterior segment complications appear to be more likely to occur if there is an underlying associated disease. The presence of complications does not seem to affect the visual outcome in patients with chronic anterior uveitis.

Cataract Progression After Intravitreal Triamcinolone Injection
American Journal of Ophthalmology
2005;139:993-998

Intravitreal steroids are increasingly being used to treat a variety of ocular diseases. Çekiç et al. assessed cataract progression after intravitreal triamcinolone injection in a retrospective interventional case-controlled study.

Forty-two phakic eyes of 37 patients were injected one, two or three times with intravitreal triamcinolone for various indications. Noninjected phakic fellow eyes served as the control (n = 29). The mean follow-up time for single injection was 12 months, for multiple injections was 14 months and for control group was 13 months. Lens status, BCVA and refractive errors were recorded at baseline and at each follow-up examination.

At last follow-up, change in posterior subcapsular cataract and refractive error from baseline were significantly different between single triamcinolone injected eyes and the control group. For multiple injected eyes and the control eyes, change from baseline in corticonuclear cataract, posterior subcapsular cataract and refractive error were significantly different. Visual acuity did not change after single injection and in the control group, but decreased after multiple injections. Eleven study eyes and two control group eyes underwent cataract extraction during the study period. Corticonuclear and posterior subcapsular cataract progression were significantly correlated with follow-up time and number of injections.

These authors conclude that single intravitreal triamcinolone injection induces posterior subcapsular cataract development while multiple injections result in all-layer cataract progression.

Predictive Factors for Progressive Optic Nerve Damage in Chronic Open-Angle Glaucoma
American Journal of Ophthalmology
2005;139:999-1009

Martus et al. evaluated whether various types of chronic open-angle glaucoma differ in predictive factors for progression of glaucomatous optic nerve damage.

This prospective observational cohort study included 517 eyes of 300 Caucasian patients. They had chronic open-angle glaucoma with either elevated IOP (primary open-angle glaucoma, n = 289; secondary open-angle glaucoma, n = 50) or normal IOP (n = 178). During follow-up (median: 49 months), all patients underwent repeated evaluation of color stereo optic disc photographs and white-on-white visual field examination.

Progression of glaucoma was defined as neuroretinal rim loss during the study period.

For patients with elevated IOP, significantly predictive factors for eventual progression were older age, advanced perimetric damage, smaller neuroretinal rim and larger area of beta zone of parapapillary atrophy. In contrast, in the normal IOP group, a significant predictive factor was presence of disc hemorrhages at baseline. Within the patients with elevated IOP, the primary open-angle glaucoma group and the secondary open-angle glaucoma group did not differ in predictive factors for progression of glaucoma.

The authors conclude that open-angle glaucoma patients with normal IOP and open-angle glaucoma patients with elevated IOP differ in predictive factors for eventual progression of glaucomatous optic nerve damage. This may have implications for pathogenesis and treatment.

Evaluating the Accuracy of Diagnostic Tests in Glaucoma
American Journal of Ophthalmology
2005;139:1010-1018

Progressive change in optic disc appearance has been suggested as the best available reference standard for glaucoma diagnosis.

Medeiros et al. evaluated the accuracy of scanning laser polarimetry with variable corneal compensation to discriminate patients with documented progressive optic disc change from healthy subjects in an observational case-control study.

Glaucoma patients with documented evidence of progressive optic disc change as assessed by stereoscopic photographs were selected. Healthy control subjects had normal visual fields and normal clinical examination. All subjects underwent imaging with the GDx VCC scanning laser polarimeter. The investigators calculated receiver operating characteristic curves, sensitivities at fixed specificities and likelihood ratios.

Sixty-five eyes were healthy control eyes. Seventy-one eyes had progressive optic disc change, of which 41 (58 percent) had abnormal visual field tests closest to the imaging date (perimetric glaucomatous optic neuropathy [GON]) and 30 (42 percent) had normal visual fields (preperimetric GON). The GDx VCC parameter nerve fiber indicator performed best for discrimination between perimetric GON and normal eyes as well as for the discrimination between preperimetric GON and normal eyes.

Scanning laser polarimetry differentiated patients with documented progressive optic disc change from normal subjects and detected abnormalities in patients with confirmed diagnosis of preperimetric GON. The authors conclude that this technique may be useful for early glaucoma diagnosis. The authors suggest that progressive optic disc change should be used in the evaluation of diagnostic accuracy of imaging instruments for glaucoma.

Acute Endophthalmitis Following Cataract Surgery
Archives of Ophthalmology
2005:123:613–620

In a systematic review of the English-language literature addressing complications of cataract surgery, Taban et al. found that the rate of endophthalmitis has not remained static. From 1963 through 1991, the rate of endophthalmitis showed a downward trend; from 1992 on, the rate increased.

The increase in the rate of endophthalmitis beginning in 1992 is temporally associated with the introduction of clear corneal surgery, suggesting a possible association between sutureless corneal surgery and postoperative infection. In those studies detailing the incision location in eyes with postoperative infection, endophthalmitis occurred roughly twice as frequently after clear corneal surgery as after scleral tunnel or limbal incisions. 

In summary, this systematic literature review suggests, but does not prove, an increased risk of endophthalmitis complicating clear corneal cataract surgery.

Cyclosporin vs. Tacrolimus for the Treatment of Uveitis
Archives of Ophthalmology
2005:123:634–641

Murphy et al. assessed the efficacy and safety of two calcineurin-inhibitors—cyclosporin A and tacrolimus—for the treatment of noninfectious intraocular inflammation in 37 patients.

The results of this two-centered randomized open-labeled study showed that both cyclosporin and tacrolimus are equally effective in suppressing ocular inflammation.  While there was no recorded difference in either quality of life or vision-related questionnaire results between treatments, tacrolimus displayed better patient tolerance with fewer side effects and positive benefits toward cardiovascular risk, whereas cyclosporin signficantly raised the serum cholersterol and mean arterial blood pressure.

Tacrolimus offers an acceptable alternative to cyclosporin in suppression of noninfectious posterior uveitis, particularly given its superior side-effect profile.

Need for Eye Care Among Seniors With Diabetes Mellitus in Fee-for-Service vs. Managed Medicare
Archives of Ophthalmology
2005:123:669–675

Brown et al. examined whether rates of need for eye care differed for adults with diabetes who had different types of health insurance—network model Medicare+Choice or fee-for-service Medicare. The study participants were all older than 65 years of age and were in Los Angeles County. 

Study ophthalmologists, who were masked to the participants’ type of health insurance, performed standardized dilated eye examinations and indicated the need for ophthalmic care during the next six months. 

The 311 Medicare+Choice and 107 fee-for-service respondents reported comparable rates of eye care provider visits and preexisting eye diseases. They also had similar HbA1c and blood pressure levels. However, in multivariate analyses, 42 percent of those enrolled in Medicare+Choice required further treatment during the next six months compared with 24 percent of the fee-for-service participants (P = 0.01).

In summary, the researchers found high rates of untreated eye disease among Medicare beneficiaries who were enrolled in both fee-for-service and Medicare+Choice, but significantly higher need for care among the latter.

Second Primary Cancers After Treatment of Choroidal Melanoma
Archives of Ophthalmology
2005:123:601–604

The Collaborative Ocular Melanoma Study Group has published COMS Report No. 25.

The researchers analyzed data from 2,320 patients enrolled in the COMS randomized trials to report sites of second primary cancer and the time to first diagnosis during routine follow-up after treatment for choroidal melanoma. 

A total of 222 patients was subsequently diagnosed with a second primary cancer other than basal or squamous cell skin cancer. The Kaplan-Meier estimate of developing a second primary cancer by five years was 7.7 percent (95 percent CI: 6.6 to 9.9 percent), similar to the rate of 8 percent for developing invasive cancer between ages 40 and 59 for men and women calculated by the American Cancer Society. The most common sites were prostate (23 percent of reported cases) and breast (17 percent). Twelve (5 percent) of the 222 patients were diagnosed with second primary cancers in two or more sites.   

Radiotherapy did not significantly increase the development of second primary cancers. The rate of diagnosis of second primary cancer did not differ significantly by smoking status, although the rate in former smokers was increased vs. that observed in either current smokers or those who never smoked.

In summary, this analysis does not suggest increased incidence of second primary cancer in patients treated for choroidal melanoma. However, these findings support routine post-treatment surveillance, especially for those with history of smoking, since some second primary cancers may be treated effectively if treated early.


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

Preventing Neurodegeneration in Inherited Glaucoma
Proceedings of the National Academy of Sciences (PNAS)
2005;102:4566–4571

Anderson et al. describe a “very robust and reproducible” neuroprotective treatment for inherited glaucoma—combining high-dose radiation with bone marrow transfer to prevent neurodegeneration in a mouse model.

In the study, glaucoma prone DBA/ 2J mice received a single treatment of high-dose g-irradiation accompanied by syngeneic bone marrow transfer at 5 to 8 weeks of age. The mice were protected from glaucomatous retinal ganglion cell degeneration to 14 months of age. This was in contrast with the majority of untreated DBA/2J mice, which experienced severe and essentially complete retinal ganglion cell degeneration by 12 to 14 months of age.

To determine if these results were reproducible, the investigators treated three groups of mice at different times with essentially the same outcomes.

The authors assert that the beneficial effect of treatment including high-dose radiation is “unprecedented,” noting that this treatment represents another tool for studying basic research into mechanisms of neuroprotection. They call for further studies to test this treatment’s ability to shield against additional models of glaucoma and other neurodegenerative diseases.

Conjunctival Epithelial Involvement by Eyelid Sebaceous Carcinoma
Ophthalmic Plastic and Reconstructive Surgery
2005;21:92–96

According to a report by Shields et al., conjunctival epithelial involvement by sebaceous carcinoma continues to pose diagnostic and therapeutic challenges for ophthalmologists and pathologists because of its tendency to masquerade either as benign or as  other malignant conditions. The researchers present a retrospective review of 60 patients with histopathologically confirmed sebaceous carcinoma of the eyelids. Epithelial involvement of the conjunctiva was identified in 47 percent of these cases—mostly in the superior tarsal and fornical conjunctiva, and less often in the inferior tarsal conjunctiva, caruncle and cornea.

The report notes that well-planned map biopsies of the conjunctiva in these patients may help tailor more specific treatment. Specifically, if the lesion is confined to the epithelium, cryotherapy and topical chemotherapy may initially be effective.

Surgeons may want to consider newer surgical excision techniques, rather than exenteration, if the tumor extends into the conjunctival stroma. However, long-term studies may be necessary to determine if this approach improves survival rate for patients with conjunctival epithelial involvement of sebaceous
carcinoma.



A Potential Treatment for Tuberculosis
New England Journal of Medicine
2005;352:933–934

Eric J. Rubin reports on a recent study by Andries et al. that proposes a new compound called R207910 as a potential treatment for Mycobacterium tuberculosis (Science 2005;307: 223–227).

Andries et al. looked for compounds that could inhibit the growth of either specific bacterial species or those that are more broadly active, and developed the candidate compound R207910. They tested the compound in mice that had been infected intravenously with M. tuberculosis. After waiting 12 days to allow the bacteria to grow, they divided the mice into two groups and treated them with a three-drug regimen containing either isoniazid or R207910.

After two months of treatment, the mice that had received the regimen containing R207910 had no detectable microorganisms. Rubin notes that Andries showed the new compound was active against several drug-resistant strains of M. tuberculosis, was not toxic in mice and could eradicate the infection more rapidly and effectively than traditional drug combinations. 

While these findings do not guarantee R20910 will prove a successful antibiotic, Rubin called it the “most promising new antituberculosis agent that has been identified in many years.”

Topical Pimecrolimus and Tacrolimus in Atopic Dermatitis
British Medical Journal
2005;330:516

Topical pimecrolimus and tacrolimus are two immunosuppressive treatments for atopic dermatitis that were developed to serve as alternatives to topical corticosteroids without the adverse events. They work by inhibiting calcineurin in the skin, which regulates the activity of several transcription factors that control cell division and trigger the early stages of T cell activation. Ashcroft et al. conducted a systematic review and meta-analysis of randomized controlled trials to determine the efficacy and tolerability of these new drugs.

They found that tacrolimus 0.1 percent was as effective as potent topical corticosteroids and more effective than mild topical corticosteroids. Yet pimecrolimus was less effective than betamethasone valerate 0.1 percent, a commonly used potent topical corticosteroid.

The authors express concern that without studies demonstrating long-term safety gains of these drugs, any advantage over current treatment regimens remains unclear. The usefulness of these alternatives in patients who failed topical corticosteroid therapy is also unclear. They call for long-term studies of these drugs—especially in light of the theoretical risk of visceral and skin cancers from preclinical studies in animals.


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

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