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Journal Highlights
New Findings from Ophthalmology, AJO and Archives
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December’s Ophthalmology:

November’s American Journal of Ophthalmology:

October’s Archives of Ophthalmology:

Roundup of Other Journals:



Smoking and Strabismus Surgery in Thyroid Eye Disease
December’s Ophthalmology

A study by Rajendram et al. confirms the association between thyroid eye disease and smoking; moreover, the authors found that the percentage of smokers among patients presenting for treatment of thyroid eye disease (52 percent) was nearly double that of smokers in the adult population of England (27 percent). In addition, this is the first study of thyroid eye disease to demonstrate that smoking at presentation increased the hazard ratio for strabismus surgery approximately twofold, independent of the indication for decompression.

The investigators conducted a retrospective review of clinical case notes between 1997 and 2002 at Moorfields Eye Hospital. Of 501 patients seen during the study period, 425 (85 percent) sets of notes were available for review; among those, initial smoking status was recorded for 378 (89 percent) patients, of whom 196 (52 percent) were active smokers. Of the smokers, 51 of 196 (26 percent) underwent strabismus surgery, compared with 19 of 138 (14 percent) nonsmokers and 7 of 44 (16 percent) ex-smokers.

Although there are no prospective data about the effects of smoking cessation on these patients, findings from this study indicate that clinicians would perform a valuable service for their patients by informing them that smoking increases the frequency of ongoing rehabilitative surgery in thyroid eye disease.

In addition, smoking should be strongly discouraged in individuals with Graves disease who either are at risk for thyroid eye disease or are already experiencing eye problems.

Sunken Upper Eyelids and Ocular Surface Morbidity
December’s Ophthalmology

Although orbital volume deficiency has been explored in terms of improving cosmetic appearance, Liang et al. focus on the clinical implications, showing that “sunken upper eyelids” or “sunken globe” can be associated with an ocular surface morbidity that extends to sight-threatening corneal epithelial breakdown.

In this retrospective case study, the investigators found various ocular surface deficits that correlated with incomplete eyelid blinking and closure, causing exposure problems not only during the day when the eye is open but also during sleep when the eye is closed.

The investigators compared a study group of 38 patients with sunken upper eyelids to a control group of 26 patients. Tearing and mucous buildup tended to be more common in the study group and tended to be worse in the morning. The study group also presented more frequently with incomplete blinking, incomplete closure, abnormal Bell phenomenon, lid/punctum ectropion and delayed tear clearance. In addition, corneal epithelial breakdown was more common in the study group and more serious in the severely affected eyes.

The authors recommend conducting further imaging and functional studies in an effort to develop new therapies to better manage corneal surface breakdown in elderly patients with complex ocular surface diseases.

Newly Identified Genes Studied in Open-Angle Glaucoma
December’s Ophthalmology

Researchers have previously established that three genes—MYOC, OPTN and WDR36—are associated with open-angle glaucoma (OAG). Recently, through genome-wide association studies, scientists have discovered three genetic variants—ATOH7, CDKN2B and SIX1—that are implicated in vertical cup-to-disc ratio and consistently associated with OAG across populations.

Ramdas et al. determined to what extent variants in the established genes and the newly identified genetic variants contributed to the risk of OAG. They found that although the new common variants all contributed significantly to OAG risk, only one of the established genes did. In addition, the authors found that participants carrying a high number of risk alleles had about a threefold increase in OAG risk compared with those who had a low number of risk alleles.

In this study, MYOC was the only established gene consistently associated with OAG. However, when the two other established genes (OPTN and WDR36) combined with MYOC, participants carrying a high number of risk alleles of common variants within these genes had a significantly increased risk of OAG. The addition of the newly identified genes significantly contributed to the prediction of OAG.

The authors concluded that, given these findings, genetic counseling has the potential to one day play a key role in helping address challenging diagnostic cases of OAG.

American Journal of Ophthalmology

Photodynamic Therapy vs. Intravitreal Ranibizumab for Central Serous Chorioretinopathy
November’s AJO

Bae et al. found that the effect of ranibizumab injections was not promising compared with low-fluence photodynamic therapy (PDT) in terms of anatomic outcomes in patients with chronic central serous chorioretinopathy.

In a prospective, randomized, single-center pilot study, the authors reported the six-month outcome comparison of the efficacy and safety of low-fluence PDT compared with intravitreal injections of ranibizumab. Sixteen eyes with chronic central serous chorioretinopathy were randomized to receive either low-fluence PDT or intravitreal injections of ranibizumab. Rescue treatment was considered if subretinal fluid remained after completion of primary treatment: low-fluence PDT for the ranibizumab group and ranibizumab injection for the low-fluence PDT group.

At three months, the mean excess foveal thickness was reduced from 74.1 µm to –35.4 µm in the low-fluence PDT group, and from 26.3 µm to –23.1 µm in the ranibizumab group. After a single session of PDT, six eyes (75 percent) in the low-fluence PDT group achieved complete resolution of subretinal fluid and reduction of choroidal hyperpermeability, whereas two (25 percent) eyes in the ranibizumab group achieved this result after consecutive ranibizumab injections. Four eyes (50 percent) in the ranibizumab group underwent additional low-fluence PDT and attained complete resolution. At three months, statistically significant improvement of BCVA was not demonstrated in the low-fluence PDT group, whereas it was observed in the ranibizumab group.

Corneal Arcus as Sign of Cardiovascular Disease
November’s AJO

Ang et al. determined that corneal arcus is associated with cardiovascular disease in ethnic Indian adults—even in those at low risk for vascular disease.

In this population-based, cross-sectional study, the authors focused on 40- to 80-year-old ethnic South Asian Indians in Singapore. The authors obtained a 75 percent response rate (3,397 of 4,497). All participants underwent standardized interviews and systemic and ocular examinations, followed by nonfasting blood sampling. Corneal arcus was detected using a standardized slit-lamp examination. The main outcome measure was cardiovascular disease, defined from a self-reported history of previous myocardial infarction, angina or stroke.

Corneal arcus—found in 1,701 (50 percent) participants—was associated with older age, male gender, higher levels of total cholesterol, hypertension and cigarette smoking. Corneal arcus was associated with cardiovascular disease independent of the above-named cardiovascular risk factors. Participants with low-risk Framingham scores were more likely to have cardiovascular disease if they had corneal arcus. Corneal arcus was also associated with cardiovascular disease independent of the Framingham score.

Argon Laser Trabeculoplasty in the Early Manifest Glaucoma Trial
November’s AJO

Heijl et al. analyzed reduction of IOP by argon laser trabeculoplasty (ALT) in the Early Manifest Glaucoma Trial and found that IOP prior to ALT markedly influenced the IOP reduction induced by ALT. The authors found a much larger reduction in eyes with higher IOP before ALT. According to the study, the treating surgeon also had a significant impact on ALT outcome.

This cohort study was based on 127 patients from the treatment group of the Early Manifest Glaucoma Trial. Patients received a standard treatment protocol (topical betaxolol hydrochloride followed by 360-degree ALT) and then were followed prospectively at three-month intervals for up to eight years. One eye per patient was included in the analyses. The authors investigated the relationship between IOP before ALT and subsequent IOP reduction, and other factors that might have influenced the effect of ALT, including stage of the disease, trabecular pigmentation, presence of exfoliation syndrome and treating surgeon.

The mean IOP before ALT and after betaxolol treatment was 18.1 mmHg, and the mean short-term IOP reduction three months after ALT was 2.8 mmHg. The IOP before ALT strongly affected IOP reduction; each 3-mmHg increase in IOP before ALT was associated with an additional mean IOP reduction of approximately 2 mmHg. The treating surgeons also had a significant impact on IOP reduction, with mean values ranging from 5.8 to –1.3 mmHg.

Archives of Ophthalmology

Bilateral Acute Iris Transillumination
October’s Archives

Tugal-Tutkun et al. described a series of patients with bilateral acute iris transillumination (BAIT) associated with pigment dispersion into the anterior chamber. They found that BAIT is not an adverse effect of oral moxifloxacin treatment as previously reported but may represent a new entity or a more severe variant of bilateral acute depigmentation of the iris, a recently described condition of unknown etiology. The authors also draw attention to the risk of early refractory IOP rise in patients with BAIT.

In this retrospective analysis, the authors examined 26 patients seen at four centers in Turkey and one in Belgium between March 2006 and July 2010. All patients (20 women, six men; mean age, 43.2 years) had simultaneous bilateral and mostly symmetrical involvement.

The typical presentation was an acute onset of red eyes and severe photophobia following a flu-like illness. There was a history of systemic antibiotic use in 19 patients (73 percent), including moxifloxacin in nine patients (35 percent). Fourteen patients (54 percent) had an IOP rise at one week. Three of these patients required surgical intervention at three weeks after onset.

Diagnostic laboratory test results, including viral serologic analyses in 10 patients, were within normal limits. Intraocular fluid analysis was not done. Initial ocular findings included pigment keratic precipitates (40 percent), circulating pigment in the anterior chamber (87 percent), iris transillumination (100 percent), mydriatic pupils poorly responsive or unresponsive to light and near stimuli (88 percent), pupil distortion (62 percent) and pigment deposition in the trabecular meshwork (100 percent). Despite the absence of inflammatory cells, anterior chamber flare was markedly elevated, especially in eyes with high-grade pigment dispersion. Although topical corticosteroid therapy resulted in immediate relief of ocular symptoms, pigment dispersion persisted for up to 18 months.

Nail Bed Hemorrhage as Clinical Marker of Optic Disc Hemorrhage
October’s Archives

The nail bed provides opportunities to view capillaries directly, and nailfold capillaroscopy is considered one of the best diagnostic imaging techniques for studying the microcirculation in vivo. Park et al. found that nailfold capillaroscopy may provide valuable information about glaucoma patients and help identify those who are more vulnerable to vascular insufficiency.

Participants in this study included 108 glaucoma patients and 38 controls. In glaucoma patients, 55.6 percent showed dilated vessels by nailfold capillaroscopy, 35.2 percent showed loss of capillaries and 19.4 percent showed nail-bed hemorrhages. Patients in the glaucoma group showed significantly more nail-bed hemorrhages than those patients in the control group.

By multivariate logistic regression analysis, avascular area and nail-bed hemorrhage continued to be independently associated with the presence of disc hemorrhages in glaucoma patients. According to the authors, this finding suggests that glaucoma patients with optic disc hemorrhage have considerable peripheral vascular insufficiency

Malignant Lymphoma of the Lacrimal Gland
October’s Archives

Rasmussen et al. evaluated the clinicopathologic features of lacrimal gland lymphoma in a retrospective national registry study. They found that malignant lymphoma of the lacrimal gland is relatively rare and occurs mostly in elderly women. Moreover, the majority of lacrimal gland lymphomas are low-grade, and the prognosis is relatively good. The distribution of lymphoma subtypes in the lacrimal gland differs from that of other ocular adnexal region lymphomas and seems to resemble that of the salivary glands.

The researchers identified 27 patients with lacrimal gland lymphoma in Denmark from January 1975 through December 2009. The majority of patients were women (70 percent), and the median age was 69 years. Extranodal marginal zone lymphoma was the most frequent lymphoma subtype (37 percent). However, the frequency of extranodal marginal zone lymphoma of the lacrimal gland was lower than the frequency of lymphoma elsewhere in the ocular adnexal region. On the other hand, the frequency of follicular lymphoma seems to be higher in the lacrimal gland (19 percent) than in the ocular adnexal region.

Twenty-two patients (81 percent) were diagnosed as having localized disease (stage 1 or 2), and five patients (19 percent) had widespread disease (stage 3 or 4). Overall five-year survival was 100 percent in follicular lymphoma, chronic lymphocytic leukemia/ small lymphocytic lymphoma, and mantle cell lymphoma; 75 percent in extranodal marginal zone lymphoma; and 25 percent in diffuse large B-cell lymphoma. For the entire study group, the five-year survival was 70 percent.

Ophthalmology summaries are written by Lori Baker Schena, EdD, 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.

More Online

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American Journal of Ophthalmology:

Archives of Ophthalmology:

Roundup of Other Journals

Slightly Elevated IOP in Premature Infants
Journal of the American Association for Pediatric Ophthalmology and Strabismus

Uva et al. have found that premature newborns can experience slightly elevated IOP compared with full-term newborns—even without having any signs of congenital glaucoma—due to an increased central corneal thickness (CCT).

The authors examined 33 premature infants and 33 full-term newborns. The examination included biomicroscopy with a handheld slit lamp, determination of corneal diameter, and dilated ophthalmoscopy by binocular indirect ophthalmoscope. They measured IOP with a tonometer, using topical anesthesia. The authors found that the mean IOP was 18.9 ± 3.77 mmHg in the premature newborns and 17 ± 2.6 mmHg in the full-term newborns. In addition, the mean CCT was 599 ± 36 µm in the premature group and 576 ± 26 µm in the full-term infants. A multivariate analysis revealed that IOP rose with increasing CCT, while CCT declined with increasing birth weight.

Propranolol Effective in Treating Infantile Hemangiomas
Archives of Dermatology
Published online Aug. 15, 2011

In a multicenter, retrospective chart analysis, Price et al. found that propranolol is more clinically effective and more cost-effective than oral corticosteroids in treating infantile hemangiomas. The propranolol treatment, which involved a daily cumulative dose of 2 mg/kg of propranolol, not only proved more effective in clearing the lesion but also required fewer surgical interventions after treatment and showed superior tolerability with minimal adverse effects. In terms of cost-effectiveness, use of propranolol resulted in a cost reduction of more than 50 percent per patient.

The study involved 110 patients with infantile hemangiomas who were classified into two groups: those who experienced clearance of 75 percent or more and those with less than 75 percent clearance. The patients were treated for a mean of 7.9 months with propranolol and 5.2 months with oral corticosteroids. Results showed that 56 of 68 of the propranolol patients (82 percent) experienced clearance of 75 percent or more compared with 12 of 42 oral corticosteroid patients (29 percent).

Mozart Effect and Glaucoma Patients Undergoing Visual Field Tests
Investigative Ophthalmology & Visual Science
Published online Aug. 9, 2011

The Mozart effect states that listening to Mozart’s “Sonata for Two Pianos in D Major” can temporarily increase temporal-spatial reasoning. In the past, clinical ophthalmologists have tried to use the Mozart effect to improve visual field test reliability. In this study, Shue et al. found that the Mozart effect did not improve the reliability of the Humphrey visual field (HVF) testing to a statistically significant degree, nor did it improve the rate of fixation losses, false positives and false negatives in patients with glaucoma.

For this study, 160 patients, aged 40 to 80 years, were randomized to three different groups for 10 minutes before HVF testing: control patients, who used no headphones or music; patients who used noise-canceling headphones but did not listen to music; and patients who listened to Mozart’s “Sonata for Two Pianos in D Major.” After the 10-minute treatment, the patients had HVF testing in both eyes. The rate of fixation losses, false positives and false negatives did not differ significantly among the three groups, nor were any improvements seen in the Mozart group. Interestingly, however, 65 percent of the participants in all groups said they would like to listen to Mozart’s music prior to future visual field tests.

Cilia-Related Gene Identified as a Cause of Retinitis Pigmentosa
Proceedings of the National Academy of Sciences
Published online Aug. 8, 2011

Tucker et al. used exome sequencing and analysis of induced pluripotent stem cells (iPSCs) to identify male germ cell–associated kinase (MAK) as a cause of retinitis pigmentosa (RP). In particular, they found that the Alu insertion into exon 9 of MAK causes autosomal recessive RP. The investigators observed the variant 43 times among 3,596 alleles of unrelated RP patients and did not observe the variant among 5,904 alleles of unrelated individuals without photoreceptor disease.

The analysis of iPSCs also indicated that the Alu insertion in MAK resulted in the loss of a conserved retinal isoform. It is known that MAK is involved in cilia-length regulation in photoreceptors, and its loss is known to cause photoreceptor death in mice. In addition to demonstrating the use of iPSCs to efficiently evaluate the pathogenicity of specific mutations in difficult-to-reach tissues, such as the retina, this particular study also revealed gaps in the current methods of disease gene discovery. By closing these gaps, researchers could have the opportunity to accelerate the effort of identifying all genes responsible for inherited disease.

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

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