American Academy of Ophthalmology Web Site: www.aao.org
New Findings from Ophthalmology, AJO and Archives
October ’s American Journal of Ophthalmology:
August’s Archives of Ophthalmology:
Roundup of Other Journals:
In a retrospective cohort study of 45,082 veterans who underwent cataract surgery in the Veterans Health Administration, Greenberg et al. found that the risk of 90-day mortality after this procedure is low—even for patients with the gravest comorbidities.
Demographic data indicated that 97.6 percent of the veterans were men, the mean age was 71.8 years and 5 percent of the veterans underwent complex cataract surgery. Using the Charlson Comorbidity Index (CCI), the researchers found that patients’ most frequent systemic comorbidities were diabetes mellitus, chronic pulmonary disease, malignant neoplasm and congestive heart failure. The overall 90-day mortality rate was 7.1 per 1,000 patients. Independent predictors of 90-day postoperative mortality included age of 80 years or older, CCI score of 2 or greater, one or more hospitalizations in the past year, chronic pulmonary disease, cirrhosis, multiple myeloma or leukemia, and metastatic solid tumor.
The researchers conclude that these low mortality rates indicate cataract surgery should be considered in older and/or sicker patients in the context of improving or maintaining quality of life and visual function.
A five-year retrospective, population-based study by Lin et al. has shown that untreated hypothyroidism is a significant predictor for the development of open-angle glaucoma (OAG). However, levothyroxine appears to have a protective effect.
The study involved 257 patients with hypothyroidism and a comparison group of 2,056 patients without hypothyroidism. The latter had no diagnosis of glaucoma before 2001. The data—gathered from the Taiwan Longitudinal Health Insurance Database—revealed that OAG developed in 7.4 percent of patients with hypothyroidism and 3.8 percent of patients in the comparison group during the five-year period. This significantly higher risk remained after adjusting for patients’ age, gender, monthly income, comorbid medical conditions and how urban their community was. However, this association was not found in patients being treated with levothyroxine—a plausible finding given prior observations showing that IOP control and outflow facility improve after levothyroxine replacement therapy.
The authors call for more studies to determine if their findings can be replicated and to shed light on the underlying mechanisms responsible for this association.
Robman et al. conducted a two-arm, case-control study to determine the effect of elevated levels of C-reactive protein (CRP) on age-related macular degeneration as well as CRP’s joint effect with the complement factor H (CFH) polymorphism on the disease.
The study involved 312 patients with early or late AMD and 232 control participants. The study also included a group of 254 early AMD patients followed for seven years. The researchers presented evidence of an epidemiological association between late AMD with elevated CRP levels and the at-risk genotype of the CFH gene. They also found that a combination of both risk factors had a synergistic super-additive effect on the development of late AMD.
The researchers call for testing of this risk-factor combination to help predict those at high risk for AMD and its progression. These individuals would be ideal candidates for intervention studies to prevent AMD progression.
Comparative effectiveness research (CER) is a high priority on the United States’ health care agenda. The research involves ascertaining the benefits and risks of different approaches to managing a clinical condition or improving care delivery. While the medical community recognizes the need to establish CER priorities, a gap remains on how to prioritize clinical questions for CER.
Li et al. tested a framework for prioritizing clinical questions for CER using practice guidelines and a survey of clinicians. Specifically, they restated the recommendations in the 2005 American Academy of Ophthalmology Preferred Practice Patterns related to the management of primary open-angle glaucoma as 45 clinical questions. Members of the American Glaucoma Society then ranked the importance of these questions on a scale of zero to 10. Nine clinical questions were ranked as most important—four on medical intervention, four on filtering surgery and one on therapy adjustment.
The authors conclude that their framework serves as a workable theoretical model for setting CER priorities and should be tested in additional medical settings.
American Journal of Ophthalmology
Pineles et al. evaluated visual and systemic outcomes in pediatric patients with purely ocular myasthenia gravis. This was a retrospective chart review over a 16-year period with a minimum follow-up of one year. The investigators analyzed associations of demographic and clinical characteristics with disease resolution, amblyopia and development of generalized symptoms of myasthenia gravis.
Thirty-nine patients were identified with a mean age of 5.4 years and mean follow-up of 4.8 years. Fifteen patients were treated with pyridostigmine only; steroid treatment was added to pyridostigmine in 19 cases. In addition, 15 patients underwent thymectomy. Four patients received steroid-sparing immunosuppressive therapy.
Resolution occurred in 10 patients, and generalized symptoms eventually occurred in nine patients. Although 10 patients were treated for amblyopia, only one had amblyopia at the final visit. There was no correlation between sex or age with amblyopia or development of generalized symptoms. Thymectomy—when performed before the onset of generalized symptoms—showed a trend toward protection from the development of generalized symptoms.
In this series, 23 percent of patients had generalized symptoms and 26 percent had disease resolution. The latter cohort confirms previous findings that treated and untreated pediatric patients with ocular myasthenia gravis have a relatively low risk of developing generalized symptoms and that related amblyopia is readily reversible. Although the treatments were more aggressive than those previously reported, the rates of amblyopia and development of generalized symptoms are comparable.
In order to identify gaps in knowledge, Lu et al. performed a literature review and analyzed observational studies that focus on the use of glaucoma medications.
The investigators reviewed electronic databases—Medline, Embase and PubMed—for English language articles published through December 2009 that contained the following search terms: physician’s practice patterns, drug prescriptions, pharmaceutical services, medication adherence, ophthalmology, glaucoma and ophthalmic solutions. The authors categorized studies by areas of focus and extracted and summarized the following key features: study population, data sources and main findings.
The authors identified 2,224 articles in the search. Fifty-five articles described glaucoma medication-use using large databases. Predominant areas of focus were: trends in prescription choices; adherence, persistence or both; rational use of medications; and policy-related issues.
The literature review showed that use of beta-blockers and miotics has decreased substantially over the last decade, whereas new agents, particularly prostaglandin analogs, have become more popular. The review also found that nonadherence was an issue in more than 25 percent of patients and that a significant proportion of patients with comorbidities, contraindications or both had received topical beta-blockers. Most articles in the review focused on adherence to glaucoma medications and changes in treatment choices.
Major gaps in knowledge include prescribing patterns by prescriber specialty (ophthalmologists, primary care physicians and optometrists), medication-related problems and subsequent adverse health outcomes. Well-designed longitudinal observational studies addressing these gaps are warranted to improve patient safety.
Saka et al. examined the long-term changes of the axial length in adults with high myopia in an open-label, consecutive, retrospective case series.
The investigators studied the medical records of 101 patients (184 eyes) with high myopia (myopia greater than or equal to –6 D, or axial length greater than or equal to 26.5 mm). Axial length was measured by A-scan ultrasonography. The authors determined the significance of the changes in the axial length during follow-up as well as the effects of age, axial length and the presence of a posterior staphyloma at the initial examination on the axial-length elongation.
The mean follow-up period was 8.2 years. The median axial length of the 184 eyes increased significantly from 28.6 mm at the initial examination to 29.4 mm at the final examination. The axial length remained stable in 69 percent of the eyes, whereas the axial length increased by more than 1 mm in 31 percent of the eyes. Of this 31 percent, the median axial length increased by 1.55 mm. An increase of the axial length per year was significantly greater in older patients than their younger cohorts, and the axial-length increase in eyes with a posterior staphyloma was significantly greater than in eyes without a staphyloma. Multiple regression analyses showed that the axial-length elongation was positively and significantly correlated with patient age at the initial examination.
The study found that in highly myopic adult patients, the axial length continued to increase. Older individuals with posterior staphyloma were more susceptible to having a greater increase in the axial length. And a progression of posterior staphyloma with increasing age is considered a key factor for the continuous increase of axial length in adults with high myopia.
Holekamp et al. evaluated whether diabetes mellitus is protective for nuclear sclerotic cataract at baseline and six and 12 months after vitrectomy surgery.
Phakic diabetic and nondiabetic patients undergoing vitrectomy surgery for a variety of retinal conditions underwent Scheimpflug lens photography in the operated and fellow eye at baseline and at six and 12 months after the surgery. Of 52 eyes included in the analysis, 23 eyes were from diabetic patients—14 of whom had surgery for ischemic retinopathy. At baseline, eyes with ischemic diabetic retinopathy had less nuclear sclerotic cataract than nonischemic diabetic and nondiabetic eyes. This was true for eyes undergoing vitrectomy surgery and for fellow eyes. Nuclear sclerotic cataract developed after vitrectomy surgery in nonischemic diabetic eyes and nondiabetic eyes at the same rate.
Diabetic eyes with ischemic retinopathy showed no significant progression of nuclear opacification and therefore had significantly less postvitrectomy nuclear cataract at six and 12 months than nondiabetic or nonischemic diabetic eyes. Normalizing to baseline opacity and adjusting for age and other comorbidities did not alter this result.
The authors conclude that ischemic diabetic retinopathy—not just systemic diabetes mellitus—protected against nuclear sclerotic cataract at baseline and after vitrectomy surgery. These findings are consistent with the hypothesis that increased exposure to oxygen is responsible for nuclear cataract formation.
Archives of Ophthalmology
Lira et al. described a case series of three eyes treated with intravitreal ranibizumab for foveal detachment secondary to macular telangiectasia type 2.
All three eyes demonstrated history of progressive vision decrease, leakage on fluorescein angiography and foveal detachment before the injection of ranibizumab. After discussing various treatment options and obtaining informed consent, the physician administered a single dose of intravitreal ranibizumab.
After six months, all eyes demonstrated better visual acuity. This improvement of visual acuity was associated with regression of foveal detachment on OCT. No treatment-related adverse effects were noted.
The authors conclude that intravitreal ranibizumab as monotherapy appears to be efficacious in the treatment of foveal detachment secondary to macular telangiectasia type 2.
Jeng et al. examined the epidemiology of ulcerative keratitis in a large, retrospective, cohort study.
Over 1 million patients were followed for a one-year period to determine the incidence of ulcerative keratitis and examine risk factors associated with ulcerative keratitis—including the roles of contact lens wear and HIV infection. Outpatient diagnosis coding was used to identify potential patients with ulcerative keratitis and chart review was performed to confirm the diagnosis. Incidence rates and potential associated risk factors were analyzed.
During the study, 302 patients experienced ulcerative keratitis, yielding an incidence of 27.6 per 100,000 person-years. In contact lens wearers, incidence of keratitis was 130.4 per 100,000 person-years, with an adjusted relative risk of 9.31 compared with non-contact lens wearers. Seven people with HIV infection developed ulcerative keratitis, of whom five were contact lens wearers. In HIV-positive patients, the incidence of corneal ulceration was 238.1 per 100,000 person-years, with an adjusted relative risk of 8.81 compared with HIV-negative patients.
The incidence of ulcerative keratitis found in this study is substantially higher than previously reported. The authors suggest this higher incidence may be due to the increasing prevalence of contact lens wear. Although increased risk of ulcerative keratitis in contact lens wear has been recognized for some time, this knowledge does not appear to have affected the occurrence of disease in the contact lens-wearing population. The high incidence of ulcerative keratitis and increased risk for patients with HIV infection are unique findings for this study.
Rutar et al. evaluated discordant clinical and pathological diagnoses involving pediatric enucleation over a 50-year period. The authors reviewed data on all pediatric enucleation specimens (in patients up to 18 years of age) analyzed between 1960 and 2008 in one institution’s eye pathology laboratory. Specimens for which the clinical diagnosis provided by the submitting ophthalmologist did not match the histopathological diagnosis were subsequently rereviewed by a different pathologist.
Out of 729 pediatric patients (746 eyes) who underwent enucleation during the study period, 29 patients and 30 eyes had discordant clinical and pathological diagnoses. All 30 of the eyes remained discordant with the original clinical diagnosis on pathological rereview. The misdiagnosis enucleation rate decreased with each respective decade studied—with the highest rate of 6.5 percent (18 of 276 eyes) in the 1960s and no misdiagnoses occurring from 1990 to 2008. Of the 369 eyes enucleated for the clinical indication of malignancy, 22 eyes were misdiagnosed in that no evidence of malignancy was found on histopathological examination. Out of the 377 eyes enucleated for benign clinical indications, seven cases were found to be malignancies by histopathology. Benign and malignant intraocular conditions simulating each other included retinoblastoma, Coats disease, nematode and bacterial endophthalmitis, panuveitis, retinal dysplasia and persistent hyperplastic primary vitreous.
The authors attribute the decreasing misdiagnosis rate over time to improvements in diagnostic techniques such as ultrasound and computed tomography. Nevertheless, this study reminds ophthalmologists of the challenges in evaluating leukocoria and blind, painful eyes in children.
Roundup of Other Journals
More than a century ago, damage to the anterior visual pathway served as one of the earliest pathological indications of multiple sclerosis. With the advent of OCT, the retina is again revealing key information about the factors that affect both inflammation and tissue atrophy in multiple sclerosis. In the largest retinal pathology series relating to multiple sclerosis, Green et al. provide a postmortem analysis of eyes from 82 patients with multiple sclerosis and 10 control patients with neurological disease.
The researchers found evidence of retinal atrophy and inflammation in the MS eyes. One previously unreported pathological finding from this series involved loss of retinal ganglion cells and neuronal loss in the inner nuclear layer, indicating that neuronal loss and atrophy includes neuronal populations that are not myelinated. And while the human retina is devoid of myelin, inflammation was prominent in the patients with multiple sclerosis and persisted in the retina at late stages of the disease. The researchers also observed a high rate of pathology in the anterior uvea, which may be the result of either direct inflammation or of the diffusion of factors from a diseased retina.
A commentary in the same issue discussed retinal nuclear loss in both the ganglion and inner nuclear cell layers and whether it is related to humoral mechanisms targeting retinal neurons or a manifestation of trans-synaptic degeneration. An examination of this relationship might result in key insights into the neuronal damage that occurs in multiple sclerosis.
Talman et al. have found that progressive retinal nerve fiber layer (RNFL) thinning occurs as a function of time in multiple sclerosis and is associated with clinically significant low-contrast letter acuity and visual acuity. The investigators conducted OCT studies of 1,304 MS patients in three medical centers who underwent OCT imaging and vision testing. RNFL thickness measurements were taken at baseline and then at six-month intervals for up to 18 months.
For those patients with less than six months of follow-up, the eyes that experienced visual loss demonstrated greater RNFL thinning than the eyes with stable vision. Over time, this RNFL thinning increased. The researchers measured average loss of 2.9 µm at two to three years of follow-up and 6.1 µm at three to 4.5 years. This thinning was observed both in eyes with and without a prior history of acute optic neuritis.
The authors conclude that these findings highlight the role of the anterior visual pathway as a potential method to assess the treatment efficacy for multiple sclerosis—especially when the patient is being treated with neuroprotective agents. The study also supports the use of OCT and low-contrast acuity in making this treatment assessment.
Public and governmental attitudes concerning physician interaction with the pharmaceutical industry have changed in recent years, with many people calling for transparency and independent regulation. Yet what are physician attitudes toward industry?
Korenstein et al. surveyed physicians and medical students across several specialties in the New York metropolitan area—receiving 590 responses. Overall, 72.2 percent said that sponsored lunches were appropriate and 25.4 percent found that large gifts were appropriate.
In terms of specialties, surgeon specialists had more favorable attitudes than physicians trained in other specialties. On the other hand, attending physicians and those who were familiar with institutional policies governing physician-pharmaceutical interaction had less positive attitudes toward industry—specifically concerning samples, meals and interactions with industry representatives.
The authors call for physician education focusing on the influence of industry, especially for trainees and surgical specialists who may be less aware of industry’s influence. This effort would help align the medical profession’s attitude with that of the nation concerning possible conflict-of-interest issues.
In an editorial at the end of the article, Jo Buyske, MD, states there is a difference between accepting tickets to a game or lunchtime sandwiches and collaborating with industry to further develop instruments and techniques. “The baby must not be thrown out with the bathwater,” said Dr. Buyske. “Physician-industry interactions are not created equal, and it is incumbent on us to be sure that policy makers and patients understand the distinctions.”
Memarzadeh et al. studied 6,130 participants of the Los Angeles Latino Eye Study who were 40 years and older and looked at the cross-sectional relationship between blood pressure, perfusion pressure and prevalence of open-angle glaucoma (OAG).
Participants completed an interviewer-administered questionnaire and a complete ocular and clinical examination. The researchers demonstrated that low diastolic, systolic and mean perfusion pressures; low diastolic blood pressure; and high systolic and mean arterial blood pressures were associated with a higher prevalence of OAG in this population. However, they did not find a relationship between the prevalence of OAG and a history of cardiovascular disease.
Since blood pressure and perfusion pressure are conditions that can be modified, the authors theorize that the risk of developing glaucomatous optic nerve damage may be reduced if patients can maintain blood pressure and ocular perfusion pressure at physiologic levels throughout the long term.