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February 2011

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

February’s American Journal of Ophthalmology:

December’s Archives of Ophthalmology:

Roundup of Other Journals:



Visual Field Loss and Progression
February’s Ophthalmology

In a retrospective study of 513 eyes of 310 primary glaucoma patients followed for an average of 6.8 years, Rao et al. found that the rate of progression in glaucoma is dependent on the severity of visual field loss at presentation. They also found that the rate of progression increases as the severity increases in the early stages of glaucoma damage, yet becomes smaller as the severity increases in the later stages of the disease.

The researchers used Guided Progression Analysis software—which provides the rate of progression of the visual field index per year—to assess the progression rate as measured by mean deviation. With this software, the percentage of visual loss at each point is calculated based on pattern deviations up to –20 dB and total deviations beyond –20 dB. The authors determined that the rate of progression worsened by 0.02 percent per year for every dB worsening of mean deviation and for every year of increasing age.

The authors theorize that their method of measuring rate of progression in eyes with severe visual field loss may be unreliable—as there could be a “ceiling effect,” which would minimize sensitivity to changes at high dB levels.

The authors call for improved methods to detect progression in eyes with severe glaucomatous damage.

Riboflavin and Ultraviolet-A Light to Treat Keratitis
February’s Ophthalmology

Khan et al. presented case studies of three patients with medically intractable Acanthamoeba keratitis who were successfully treated with an adjunctive therapy using ultraviolet-A light (UVA) and riboflavin.

While the three patients used different brands of contact lenses and solutions, they all presented with evidence of improper contact lens use. The patients received two treatment sessions involving topical application of 0.1 percent riboflavin solution to the ocular surface combined with 30 minutes of UVA irradiation on the corneal ulcer. (This treatment was given in conjunction with their conventional therapy.) After the first treatment, all patients demonstrated a rapid reduction in their symptoms and decreased ulcer size. Clinical improvement then slowed but continued after the second session. Signs of inflammation mostly resolved, with the ulcers closing within three to seven weeks of the first application.

The authors conclude that this treatment approach shows promise in appropriate candidates, and they call for further research on how to best use photochemical therapy to treat infectious keratitis.

Genetic Variant Identified for High Myopia
February’s Ophthalmology

Genome-wide association (GWA) studies can screen upward of a million single nucleotide polymorphisms spaced across the genome and are being used in the search for causal sequence genetic variants. Li et al. utilized the GWA approach to identify genetic variants that could possibly account for individual susceptibility to high myopia in Singaporean Chinese.

The authors focused on two population studies as independent data sets—the Singapore Cohort Study of the Risk Factors for Myopia and the Singapore Prospective Study Program—to identify top-ranked susceptibility markers for high myopia. A Japanese data set served as a replication cohort to confirm these markers.

Using this approach, the researchers identified a significant association of the CTNND2 gene on chromosome 5p15 with high myopia in both the Chinese and Japanese cohorts.

The authors conclude that this discovery may one day lead to the development of early intervention strategies to slow down the progression of myopia in high-risk individuals.

American Journal of Ophthalmology

Glaucoma and Corneal Graft Survival
February’s AJO

Stewart et al. evaluated whether the risk of graft failure in patients with glaucoma is dependent on the indication for penetrating keratoplasty (PK).

This retrospective cohort study included all patients on the United Kingdom Transplant Registry during a seven-year period. The patients were undergoing their first PK and had at least one year of follow-up. Data were collected regarding the indication for PK, presence and management of glaucoma, graft diameter, recipient risk factors and graft survival.

A total of 6,255 transplants in eyes without glaucoma and 1,994 in eyes with glaucoma were analyzed. Three-year transplant survival was 86 and 72 percent, respectively. Three-year survival was 73 percent in eyes with medically managed glaucoma compared with 63 percent in surgically managed glaucoma.

Glaucoma patients undergoing PK for pseudophakic bullous keratopathy or Fuchs dystrophy had significantly increased risk of graft failure. There was no equivalent significant difference for those with keratoconus, previous noncataract ocular surgery, trauma or noninfectious ulcerative keratitis. Endothelial decompensation accounted for a significantly greater proportion of graft failure in recipients with glaucoma than in those without glaucoma.

The authors conclude that the presence of glaucoma carries an increased risk of graft failure, particularly due to endothelial decompensation. This risk is dependent on the indication for PK, with transplants undertaken for primary corneal endothelial disease carrying a higher risk.

Implantation of Endoscope-Guided Posterior Chamber IOL
February’s AJO

Olsen and Pribila describe a novel method for placement of a sulcus-fixated, sutured posterior chamber intraocular lens (sf-SPC-IOL) using endoscopic guidance during pars plana vitrectomy surgery. This study was a retrospective case series by a single surgeon that included both pediatric and adult patients undergoing sf-SPC-IOL in the setting of posterior segment surgery.

Seventy-four eyes of 71 patients had pars plana vitrectomy and placement of an sf-SPC-IOL. Preoperative diagnosis included trauma (42 percent), subluxated lenses with no capsular support (24 percent), uveitis (15 percent), congenital cataract (11 percent), Marfan syndrome or ectopia lentis (6 percent) and other (2 percent). Fifty-one adults and 20 children were reviewed from cases performed from 1999 through 2007. The sf-SPC-IOL sutures were placed using endoscopic visualization of ab interno scleral fixation.

The mean follow-up time was nearly three years, and most patients experienced an improvement in visual function. Many eyes had advanced posterior segment disorders. Only two broken sutures occurred—both attributable to repeat trauma.

Advantages of this technique included excellent visualization and haptic localization, optimal lens centration, buried knots, broad scleral imbrication and minimal vitreous- and hemorrhage-related complications. Disadvantages included the learning curve, increased operative time, long-term suture stability issues and limited availability of intraocular endoscopes.

Anesthesia for Intravitreal Injection
February’s AJO

In a randomized trial, Yau et al. compared the anesthetic effectiveness of three topical agents used for intravitreal injections for neovascular age-related macular degeneration.

Patients were randomized 1:1:1 to receive one of three agents: tetracaine hydrochloride 0.5 percent drops and a lidocaine 4 percent pledget; tetracaine hydrochloride 0.5 percent drops alone; or cocaine 4 percent (with epinephrine) drops alone. Patients were asked to score their pain experience using a visual analogue scale (VAS) immediately following and 15 minutes after their injection. The average of these scores was used as the primary outcome. The physician performing the procedure separately scored his perception of the patients’ pain using the Wong-Baker FACES scale.

Means of the averaged VAS pain score for groups 1, 2 and 3 were 19, 21 and 21, respectively. Mean Wong-Baker pain scores for the groups were 1.9, 2.1 and 2.3, respectively. There was no significant difference between groups for average VAS pain score. Similarly, there was no significant difference for the physician-perceived pain score between groups.

Archives of Ophthalmology

Cryotherapy vs. Laser Photocoagulation
December’s Archives

Lira et al. compared the reattachment rate and visual acuity of patients with rhegmatogenous retinal detachment (RRD) who underwent scleral buckle surgery with retinopexy by intraoperative cryotherapy vs. laser photocoagulation performed one month postoperatively.

Eighty-six patients with RRD scheduled for scleral buckle surgery were randomly assigned to a cryotherapy or photocoagulation group. The primary outcome was the one-week reattachment rate. Other outcome measures included later reattachment rates (at one and six months), BCVA, reoperation rate and postoperative complications.

The rates of one-week, one-month and six-month anatomical success were similar in the two groups. Three patients from the cryotherapy group and two from the photocoagulation group needed one additional RRD surgery after primary failure at one-week follow-up. The types of postoperative complications were similar in both groups except for eyelid edema, which was more frequent in the cryotherapy group. Visual recovery was slower in the cryotherapy group, but the difference in visual acuity after six months was not significant.

The authors conclude that in patients with uncomplicated retinal detachment, both techniques of retinopexy have shown satisfactory anatomical and functional success. The option of laser photocoagulation offers faster visual acuity recuperation with fewer postoperative complications. However, it may require a second intervention, and it is more costly than cryotherapy.

Patching vs. Acupuncture for Anisometropic Amblyopia
December’s Archives

In a randomized trial, Zhao et al. investigated the effectiveness of two-hour daily patching vs. acupuncture in treating anisometropic amblyopia in children aged 7 to 12 years who wore optimal spectacles for at least 16 weeks.

Eighty-eight children with an amblyopic eye who had BCVA of 0.3 to 0.8 logMAR at baseline were randomized to receive two hours of patching of the sound eye daily or five sessions of acupuncture weekly for 15 weeks. All participants received constant optical correction plus one hour of near vision activities daily, and were followed up at five, 10, 15 and 25 weeks.

Mean BCVA in the amblyopic eye at 15 weeks improved from baseline by 1.83 and 2.27 lines in the patching and acupuncture groups, respectively. After baseline adjustment, the mean difference of BCVA between the two groups was 0.049 logMAR, which meets the definition of equivalence (difference of one line).

BCVA improved by two lines or more in 28 (66.7 percent) and 31 (75.6 percent) eyes in the patching and acupuncture groups, respectively, while amblyopia was resolved in seven (16.7 percent) and 17 (41.5 percent) eyes in the respective groups.

The authors conclude that acupuncture produced equivalent treatment effect for anisometropic amblyopia compared with patching. Further studies are warranted to investigate acupuncture’s clinical value in the treatment of amblyopia.

Obstructive Sleep Apnea and Retinal Vein Occlusion
December’s Archives

Glacet-Bernard et al. evaluated the possible involvement of obstructive sleep apnea (OSA) in retinal vein occlusion (RVO).

From the records of 63 patients with RVO, 30 patients with two of the three following risk factors for OSA were selected for further sleep-apnea screening: associated cardiovascular disease, snoring and daytime sleepiness. Sleep apnea was found in 77 percent of the selected patients. Although this series screened only a selected subset of a series of RVO patients, if the nonselected patients are assumed to have no OSA, the estimated prevalence in an RVO patient series would be 37 percent—still much higher than the 2 to 7 percent that would be expected in the general population.

Among the 23 positive patients, only one had a previous diagnosis of OSA; the remaining 22 patients were first recognized as having OSA as part of this study. This confirmed that there is wide underrecognition of OSA in the general population.

The authors conclude that OSA is frequent and underrecognized in RVO patients. Their findings suggest that OSA could be an additional risk factor that plays an important role in the pathogenesis of RVO or at least that it is a frequently associated condition that could be a triggering factor. This association may explain why a majority of RVO patients discover visual loss upon awakening.

Ophthalmology summaries are written by Lori Baker Schena, PhD, 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

Role of Corneal Cold Thermoreceptors in Basal Tearing
Nature Medicine
Published online Nov. 14, 2010

A hypothesis about the relationship between corneal cold thermoreceptors and basal tearing led Parra et al. to uncover a previously unidentified role for peripheral cold thermoreceptors as regulators of surface wetness of exposed body mucosae.

The authors describe how recording nerve terminal impulse activity in mouse eyes in vitro demonstrated that corneal cold thermoreceptors proved sensitive to small temperature variations and correspondingly changed their discharge. They further observed that deletion of the cold-transducing ion channel TRPM8 (transient receptor potential cation channel subfamily M member 8) in mice abrogated cold responsiveness and reduced basal tearing— all without affecting nociceptor-mediated irritative tearing. When the authors attempted to confirm whether the relationship between corneal temperature and basal tearing was also present in humans, they discovered that cornea warming decreased tearing rate.

The authors conclude that their findings could potentially open new avenues for treating not only dry eye but other idiopathic pathological conditions, including burning mouth syndrome or vaginal dryness associated with dry eye.


BAP1 Mutated in Metastasizing Uveal Melanomas

Harbour et al. focused their research on uveal melanomas, utilizing massively parallel exome sequencing—combined with Sanger resequencing—in an attempt to identify the metastasis-related mutations in this condition. The investigators analyzed two class 2 tumors that were monosomic for chromosome 3 (MM56 and MM70) and that matched normal DNA from peripheral blood lymphocytes. Both tumors contained inactivating mutations in the gene-encoding BRCA1-associated protein 1 (BAP1) located at chromosome 3p21.1.

Expanding the study, the researchers found BAP1 mutations in 26 of 31 class 2 tumors, including 15 mutations causing premature protein termination and six affecting its ubiquitin carboxy-terminal hydrolase domains. In addition, one tumor had a frameshift mutation germline in origin—thus suggesting a susceptibility allele.

The researchers conclude that these findings identify mutational inactivation of BAP1 as an important event in acquiring metastatic competence in uveal melanoma. Thus, BAP1 may represent a potential target in cancer treatment.

Polylactide Plates for Orbital Fracture Repair
Archives of Facial Plastic Surgery

Lieger et al. looked at the viability of a bioresorbable polylactide [P(L/DL)LA 70/30] implant to repair orbital wall defects. This retrospective study involved 46 patients with orbital blowout fractures with at least 1.5-cm2 bone defects in one or two walls. These defects were each reconstructed within two weeks of injury using this material.

Findings showed that the P(L/DL)LA 70/30 implant was well-tolerated and reliable in small and middle-sized defects. Specifically, none of the 46 patients demonstrated a clinical foreign- body reaction, nor was there any evidence of infection. While diplopia developed in six patients three months following surgery, this normalized at six months in five of the patients. Two patients experienced mild enophthalmos one year after surgery. In addition, the reconstructed areas did not show signs of sagging on computed tomography examination. The researchers noted that the plate left a stable bridge of healed bone or soft tissue after it completely degraded.

Management Guidelines in Cutaneous Squamous Cell Carcinoma
Archives of Dermatology

Jambusaria-Pahlajani et al. have found that no clear standard of care exists among Mohs surgeons managing high-risk cutaneous squamous cell carcinoma. High risk is generally defined as cutaneous squamous cell carcinoma where there is an elevated risk of recurrence or metastasis.

Current treatment recommendations involving radiologic nodal staging and adjuvant radiation therapy vary. Approximately 25 percent of the American College of Mohs Surgery membership completed a survey regarding either management of high-risk cutaneous squamous cell carcinoma (117 Mohs surgeons) or squamous cell carcinoma with perineural invasion (118 Mohs surgeons).

Most surgeons responded that in-transit metastasis or perineural invasion constituted the top factors that led them to consider recommending radiologic nodal staging, sentinel lymph node biopsy or adjuvant radiation therapy. However, this was where the agreement concerning treatment approaches ended. There was no consensus regarding the use of—or indications for—radiologic nodal staging, sentinel lymph node biopsy or adjuvant radiation therapy.

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


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