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Journal Highlights
New Findings from Ophthalmology, AJO and Archives
 
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Ophthalmology:

American Journal of Ophthalmology:

Archives of Ophthalmology:

Roundup of Other Journals:

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Ophthalmology

Iodine-125 Plaque Radiotherapy to Treat Iris Melanoma
Ophthalmology
Published online Nov. 30, 2011

Shah et al. found that management with custom-designed iodine-125 plaque radiotherapy was effective in controlling residual or recurrent iris melanoma after surgical resection in 87 percent of cases throughout six years of follow-up. In addition, with this management approach, enucleation was avoided in 28 of the 32 study eyes. In the four remaining eyes, tumors were not controlled, with further growth occurring at three, nine, 28 and 54 months.

The retrospective, nonrandomized, interventional case series involved 12 eyes with residual iris melanoma and 20 eyes with recurrent iris melanoma. At the beginning of the study, 84 percent of the participants presented with good VA (20/20 to 20/50), 9 percent with intermediate VA (20/60 to 20/150) and 6 percent with poor VA (less than or equal to 20/200). At six years, 9 percent had poor VA. In that same time period, radiation complications included corneal epitheliopathy in 6 percent of eyes, scleral necrosis in 3 percent, cataract in 53 percent, elevated IOP from the tumor or radiotherapy in 19 percent and macular edema in 6 percent.

The authors call these findings encouraging and recommend a definitive future study focusing on this patient group with residual and recurrent iris melanoma.


Prosthesis Effective in Managing Combat-Related Thermal Injuries
Ophthalmology
Published online Nov. 30, 2011

Kalwerisky et al. present a case series of 10 patients (16 eyes) who sustained severe periorbital thermal injuries during combat missions in Iraq and Afghanistan and were subsequently treated for exposure keratopathy with the Boston Ocular Surface Prosthesis (BOSP). The prosthesis works by providing a protective environment for the cornea when the eyelids cannot. The authors found that while the BOSP is not without risks, the prosthesis can protect the ocular surface until the patient receives more definitive treatment. In addition, the BOSP can serve as an effective drug-delivery system for unpreserved, fortified antibiotics to treat corneal infiltrates. It also is a comfortable, refractive error–correcting lens that can be custom fit for the patient.

All 10 patients included in this retrospective, interventional case series had developed vision-threatening ocular surface disease as a result of chronic ocular exposure. The mean BOSP wear time was 16 hours per day. Ocular surface rehabilitation was achieved using the BOSP, with 10 of the 16 treated eyes achieving a BCVA of 20/70 or better. Five eyes had a BCVA of 20/40 or better.

Although this study was conducted on individuals injured on the battlefield, the authors point out that the findings of this case series may be applicable to civilian level 1 trauma centers and burn units that treat similar types of thermal injuries.


Imaging System Sheds Light on Corneal Health
Ophthalmology
Published online Nov. 30, 2011

The Oculus Pentacam is a noninvasive optical device that incorporates the Scheimpflug principle to take up to 50 cross-sectional images of the entire anterior segment within two seconds. Otri et al. used this system to establish normal values of corneal density in healthy patients and to study alteration in corneal density during active and healed stages of bacterial keratitis. They found that the mean densitometry value of normal corneas in the 64 eyes of 40 healthy control patients was 12.3 ± 2.4. In the 36 eyes of 35 patients with bacterial keratitis, the densitometry values were greatest at the site of the active infection and significantly higher than in the healthy patients.

The densitometry values at the points of clear cornea farthest away from the site of infection were also significantly higher during active disease than in the healthy patients, but failed to return to normal values, even after complete resolution of the infection. Moreover, the researchers found the infiltrates’ density was much higher than that of residual scars after the ulcers healed.

The authors conclude that densitometry may prove to be a useful tool for objective measurement of the cornea’s response to both infection and therapy.


Low Risk of Acute Angle Closure After Pupillary Dilation
Ophthalmology
Published online Nov. 25, 2011

Lavanya et al. found that there is a low risk of developing primary acute angle closure (AAC) within 12 hours after a patient has had pupil dilation with 1 percent tropicamide eyedrops and has received a prophylactic dose of oral acetazolamide. More specifically, 0.64 percent of the primary angle-closure suspects (PACS) in this large cohort of Asian patients with narrow angles developed AAC. The only clinical parameter associated with a significant increase in IOP after pupil dilation was the presence of narrower angle width, as determined by gonioscopy.

This prospective clinical study involved 471 Asian PACS; 75.4 percent were women, and 92.8 percent were Chinese. Of these participants, three developed AAC within six hours of dilation, despite prophylaxis with oral acetazolamide.

According to the authors, the low risk of AAC after pupil dilation they reported in this research is consistent with previous epidemiologic studies. The authors also found that approximately 1 percent of patients developed an increase in IOP of greater than or equal to 8 mmHg in either eye after one hour.


American Journal of Ophthalmology

Higher-Order Aberrations of the Corneal Surfaces After Transplantation
February’s AJO

In eyes that have undergone corneal transplant, the refractive indices of the anterior and the posterior surfaces differ greatly depending on the type of corneal procedure performed.

Koh et al. found that eyes that underwent Descemet stripping automated endothelial keratoplasty (DSAEK) had lesser amounts of anterior corneal higher-order aberrations (HOAs) compared with eyes that underwent penetrating keratoplasty (PK) or deep anterior lamellar keratoplasty (DALK). However, the anterior and posterior corneal HOAs in DSAEK eyes were still greater than those in control eyes.

In a retrospective, case-control study, the authors investigated HOAs of the anterior and posterior corneal surfaces in 24 post-PK eyes, 28 post-DALK eyes and 19 post-DSAEK eyes; 29 normal eyes served as controls. The anterior and posterior corneal heights and pachymetric data were obtained with a Scheimpflug-based corneal topographer. Corneal HOAs for 4-mm pupils were calculated from the height data and were expanded with normalized Zernike polynomials. The resulting HOAs were compared among the procedures using the root mean square.

Control eyes had significantly lower total HOAs and Zernike vector terms of the anterior and posterior surfaces than the other groups, except for spherical aberration. The mean anterior corneal HOAs in the PK, DALK, DSAEK and control groups were 1.38 ± 0.67 µm, 1.19 ± 0.57 µm, 0.61 ± 0.33 µm and 0.21 ± 0.07 µm, respectively. The anterior corneal HOAs in the DSAEK group were significantly less than those in the PK group and DALK group. There were no significant differences in the posterior corneal HOAs among the treatment groups.

These findings may help to explain the quality of vision after these surgical techniques.


Depression Linked to Worse Visual Functioning in Patients With Ocular Inflammatory Disease
February’s AJO

In a prospective, cross-sectional survey and medical record review, Qian et al. characterized the level of depression in patients with ocular inflammatory disease and determined predictors of depression. They found that worse visual function was associated with depression.

Participants included patients with noninfectious ocular inflammatory disease in a university-based tertiary referral center. They were given the self-administered Beck Depression Inventory-II (BDI-II), National Eye Institute Visual Function Questionnaire- 25 (NEI VFQ-25) and additional supplemental questions. The investigators reviewed medical records for clinical characteristics and conducted univariate analyses to compare clinical characteristics between patients with and without a positive screen for depression.

The investigators also performed a multivariate regression model to determine the most significant predictors of depression.

Of the 104 participants, 26.9 percent screened positive for depression with the BDI-II. Of the depressed group, only 39.3 percent had been previously diagnosed with depression. NEI VFQ-25 scores were significantly lower in depressed patients in all subscales except driving and color vision.

Predictors of depression were inadequate emotional support, lower visual functioning (VFQ composite score), history of changing immunomodulatory treatment and current oral corticosteroid use.

The authors recommend heightened awareness of potential depression in patients with ocular inflammatory disease.


Subconjunctival Bevacizumab Not as Effective as Mitomycin C as Adjunctive to Trabeculectomy
February’s AJO

Niforushan et al. found that adjunctive subconjunctival bevacizumab with trabeculectomy was effective in controlling the IOP profile, but its effect was less pronounced than that of mitomycin C (MMC).

In this study, the authors compared the outcome of trabeculectomy with subconjunctival bevacizumab against that of trabeculectomy with MMC. They enrolled 36 eyes from 34 patients with uncontrolled glaucoma. Eighteen eyes underwent trabeculectomy with subconjunctival bevacizumab injection (0.2 mg/mL), and 18 eyes underwent trabeculectomy with MMC (0.02 percent for three minutes). The outcome measures were BCVA, IOP, number of IOP-lowering medications, complications and bleb morphologic features (based on the Indiana Bleb Appearance Grading Scale).

The mean follow-up times for the MMC and bevacizumab groups were 7.8 months and 7.4 months, respectively. The mean IOP in the bevacizumab group improved from 21.9 mmHg with 2.7 antiglaucoma medications at baseline to 13.6 mmHg with 0.2 antiglaucoma medications at the last visit. The mean IOP in the MMC group improved from 23.3 mmHg with 2.6 antiglaucoma medications at baseline to 9.6 mmHg with no antiglaucoma medications at the final visit. There was a statistically significant difference in mean IOP between the two groups at the last visit, favoring the MMC group.


Endophthalmitis Outbreak After Intravitreal Injection of Bevacizumab
February’s AJO

In a noncomparative, consecutive case series, Goldberg et al. report on a series of patients with Streptococcus endophthalmitis after injection with intravitreal bevacizumab prepared by the same compounding pharmacy. They found that the most likely cause of this outbreak was contamination during syringe preparation.

The investigators reviewed the medical records and microbiology results of 12 patients who presented with endophthalmitis one to six days after intravitreal bevacizumab injection administered between July 5 and July 8, 2011. The injections were performed at four different locations in southern Florida. Although none of the infections originated at the Bascom Palmer Eye Institute, nine patients presented to its tertiary-care ophthalmic emergency room for treatment, and three additional patients were seen in consultation. All patients were treated initially with a vitreous tap and injection; eight patients subsequently received a vitrectomy. Microbiology cultures for 10 patients were positive for Streptococcus mitis and oralis. Seven unused syringes of bevacizumab (prepared by the compounding pharmacy at the same time as those used in the affected patients) also were positive for these bacteria.

After four months of follow-up, all but one patient had VA of counting fingers or worse, and three required evisceration or enucleation. Local, state and federal health department officials have been investigating the source of the contamination.


Archives of Ophthalmology

Emergency Department Eye Care and Principal Payer Sources
January’s Archives

Witmer et al. studied the principal payer sources for persons receiving eye care through emergency departments (ED) in Florida and found that a substantial proportion of ED eye care is reimbursed through Medicaid or is paid out of pocket, particularly for children.

The authors used the Florida Agency for Health Care Administration to extract information on payer sources for 587,227 ED eye care visits from 2005 through 2009. Of these eye care visits, the large majority of patients received treatment in the ED (97.9 percent), with 12,105 (2.1 percent) of visits resulting in hospitalization. Commercial insurance was the most frequent payer of ED outpatient services (31.1 percent), followed by self-pay (26.2 percent) and Medicaid (22 percent). For persons younger than 18 years, however, Medicaid and self-payment made up 67.7 percent of principal payers. Statistical trends in payer coverage were difficult to assess because trends might have been driven by changes occurring during the economic recession in 2008 and 2009.


Gene Therapy for Leber Congenital Amaurosis Caused by RPE65 Mutations
January’s Archives

Jacobson et al. determined the safety and efficacy of subretinal gene therapy in the RPE65 form of Leber congenital amaurosis (RPE65-LCA) by using a recombinant adeno-associated virus serotype 2 vector altered to carry the human RPE65 gene. They found the gene therapy to be sufficiently safe to warrant advancing the treatment by extending the area of treated retina to include nasal, temporal and superior retina, and treating the preferred eye. The authors note that there was a lack of clear benefit and some risk in treating the fovea unless there was foveal atrophy and parafoveal fixation.

This was an open-label dose-escalation study of 15 patients, ages 11 to 30 years, with the first of five cohorts of patients followed for a maximum of three years after treatment.

There were no detectable systemic safety concerns, and any ocular adverse events were attributable mainly to the surgery. The treatment demonstrated efficacy in all patients of all ages, but to different degrees. The improvements in vision were localized to the treated areas. Both rod vision and extrafoveal cone vision improved. Foveal cone vision, however, did not increase. Counterintuitively, two eyes with foveal atrophy, parafoveal fixation and the lowest acuities at enrollment showed an improvement in visual acuity of greater than 15 letters after treatment. This improvement was attributed to their maintaining extrafoveal fixation loci in the treated areas.


Blockade of Pro-Lymphangiogenic VEGF-C in Dry Eye Disease
January’s Archives

Goyal et al. found that targeting corneal lymphatic ingrowth with anti-VEGF-C treatment led to significant improvement in dry eye disease (DED) in mice, reflected by a decrease in inflammation at the clinical, molecular and cellular levels. Inhibition of pro-lymphangiogenic growth factors or their receptors could thus prove to be a potential therapeutic strategy for DED.

The investigators used a well-characterized murine model of desiccating stress-induced DED. Intraperitoneal injections of anti-VEGF-C antibody were given daily from day 1 to day 13 to one group of DED mice. The researchers then evaluated corneal lymphatic ingrowth, infiltration of CD11b+ cells, expression of different inflammatory cytokines and VEGF receptors. Clinical DED was scored by corneal fluorescein staining according to the NEI grading system.

Blockade of VEGF-C led to a significant reduction in lymphatic vessel growth in the corneas of DED mice. In addition to significantly decreasing CD11b+ cells, anti-VEGF-C treatment significantly decreased mRNA expression of pro-lymphangiogenic VEGF-C, VEGF-D and VEGFR-3 in the corneas of treated mice. Significant decrease in expression of inflammatory cytokines in the conjunctiva and lymph nodes was also seen with anti-VEGF-C treatment. Moreover, VEGF-C blockade led to suppression of clinical epithelial disease, as seen by a significant decrease in corneal fluorescein uptake.
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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.


Roundup of Other Journals

Novel UVA-Sensitive Signaling Pathway in Melanocytes May Explain Skin Tanning
Current Biology
2011;21(22):1906-1911

Wicks et al. showed that human melanocytes use a novel mechanism to sense and respond to ultraviolet light. They found that UV-A light activates endogenous opsin receptors, causing calcium mobilization via a pathway mediated by G protein and phospholipase C. The authors also demonstrated that the visual photopigment rhodopsin is expressed in human epidermal melanocytes and contributes to ultraviolet-radiation (UVR) phototransduction. This finding suggests that human opsin receptors function outside the eye.

The investigators made these discoveries through a system that permits real-time imaging of cultured cells and exposure to irradiances comparable to solar UVR. Their research showed that upon UVR exposure, significant melanin production was measured within one hour, with cellular melanin continuing to increase in a retinal- and calcium-dependent manner up to fivefold after 24 hours.

They concluded that this novel UVR phototransduction mechanism may help shed light in understanding nonocular opsin signaling pathways and their role in skin physiology and pathology.


CXL Halts Keratoconus Progression, Improves Some Visual Parameters
British Journal of Ophthalmology
2011;95(11):1519-1524

In a masked, randomized, prospective bilateral study, O’Brart et al. found that corneal collagen cross-linking appears to be an effective and safe treatment modality to halt the progression of keratoconus. In addition, the investigators observed improvements in visual and topographic parameters in some eyes.

To conduct the study, the authors recruited 24 patients with early and/or moderate keratoconus and recent progression. They treated one randomly assigned eye after epithelial removal with collagen cross-linking with riboflavin 0.1 percent and UV-A light. The other eye went untreated to serve as a control. The follow-up period was 18 months.

The investigators report that, at 18 months, Orbscan 3-mm keratometry and Orbscan-simulated astigmatism, Keraton Scout–simulated astigmatism, cone apex power, root mean square, coma and pentafoil decreased in treated eyes and increased or remained unchanged in untreated eyes. In treated eyes at 18 months, BCVA improved.

The only adverse event involved a treated eye that experienced transient recurrent corneal erosions.


DVD, Brochure Optimize Cataract Surgery Informed Consent
Journal of Cataract and Refractive Surgery
Published online Nov. 7, 2011

Shukla et al. found that concise informed consent information sheets written at a second-grade reading level or a videotaped presentation helped patients to understand the risks and benefits of cataract surgery and treatment alternatives. Age, previous cataract surgery and the highest level of education did not have an effect on these findings.

The investigators randomized patients being considered for cataract surgery into one of four groups: group 1, conventional verbal information; group 2, conventional verbal information combined with a second-grade reading-level brochure; group 3, conventional verbal information combined with an eighth-grade reading-level brochure; and group 4, conventional verbal information plus the Academy’s Understanding Cataract Surgery DVD featuring an aid to informed consent.

After undergoing the informed consent process, patients filled out a 12-item questionnaire focusing on the surgical procedure, benefits, risks and alternatives. Patients in groups 2 and 4 scored significantly higher than patients in group 1 or 3.


Whole-Genome and Exome Resequencing Reveals Novel Variant Associated With Melanoma
Nature
2011;480(7375):99-105

In this study, Yokoyama et al. illustrate the value of performing whole-genome and exome resequencing to identify novel disease-specific variants and to functionally characterize variants associated with complex diseases that are otherwise not detectable through genome-wide association studies (GWAS) or linkage approaches.

The authors focused on whole-genome sequencing of probands from several melanoma families in an effort to identify other genes associated with familial melanoma. They identified a novel germline mutation of MITF, which shows a relatively strong linkage to melanoma but not a high enough signal to be clearly visible in previous GWAS. An E318K variant was significantly associated with melanoma in large case-control samples in both Australia and the United Kingdom. In the Australian sample, the variant allele was significantly overrepresented in cases with a family history of melanoma and/or multiple primary melanomas. In addition, the variant allele was associated with increased nevus count and nonblue eye color.
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Roundup of Other Journals is written by Lori Baker Schena, EdD, and edited by Deepak P. Edward, MD.



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