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April 2007

 
Journal Highlights
New Findings from Ophthalmology, AJO and Archives
 
 

April's Ophthalmology:

April's American Journal of Ophthalmology:

February's Archives of Ophthalmology:

Roundup of Other Journals:

Ophthalmology

Endothelial Cell Loss Two Years After DLEK
April?€™s Ophthalmology

Terry et al. conducted a prospective study of deep lamellar endothelial keratoplasty (DLEK) to determine endothelial survival over a two-year period.

The authors focused on two approaches: large-incision DLEK grafts where the tissue is inserted without folding and small-incision DLEK grafts where the tissue is folded prior to insertion. While initial cell loss from both types of surgery was minimally changed from six to 12 months postoperatively, an acceleration of cell loss was detected from both surgeries in postoperative year one to year two. Additionally, the small-incision DLEK technique demonstrated a significantly higher endothelial cell loss in this time period than the cell loss after large-incision DLEK surgery.

Although long-term endothelial survival after DLEK is not yet known, current evidence suggests that endothelial keratoplasty is a reasonable alternative to penetrating keratoplasty when treating endothelial disease.

Fourth-Generation Fluoroquinolones in Cataract Surgery
April?€™s Ophthalmology

Moshirfar et al. have found that 0.07 percent of patients treated with fourth-generation fluoroquinolone eye drops after uncomplicated cataract surgery experienced endophthalmitis.

Their retrospective, observational case series involved 20,013 patients who received preoperative and postoperative topical fourth-generation fluoroquinolones as anti-infective prophylaxis. During the study period, 81 percent of patients received topical gatifloxacin and 19 percent received topical moxifloxacin. Fourteen patients developed endophthalmitis (0.07 percent overall rate)?€”nine in the gatifloxacin group and five in the moxifloxacin group, a difference that was not statistically significant. Vitreous cultures were positive in 10 of the cases, with coagulase-negative staphylococci followed by Streptococcus species serving as the most commonly isolated organisms.

The authors acknowledge that this was a retrospective study and the design excluded complicated cases. They conclude that the 0.07 percent rate of en- dophthalmitis was within the range of previously reported incidence rates.

Varicella-Zoster Virus Linked to Acute Retinal Necrosis
April?€™s Ophthalmology

In a retrospective study of 22 HIV-negative patients with acute retinal necrosis, Lau et al. found that the condition was most commonly caused by varicella-zoster virus, followed by herpes simplex virus. The Epstein-Barr virus may also play a role. All of the eyes that were positive for Epstein-Barr virus were also positive for varicella-zoster virus.

In light of these findings, the researchers conclude that patient management should include prompt diagnosis, prophylactic argon laser retinopexy (if possible, within the first two weeks to reduce retinal detachment risk), and systemic acyclovir and corticosteroids.

Intravitreal Bevacizumab Shows Promise in Diabetic Macular Edema
April?€™s Ophthalmology

Six-month follow-up results from the Pan-American Collaborative Retina Study Group indicate that primary intravitreal bevacizumab (Avastin) injections of 1.25 mg or 2.5 mg in patients with diabetic macular edema (DME) appear to provide stability and improvement in visual acuity, optical coherence tomography readings and fluorescein angiography tests at six months.

Arevalo et al. reviewed clinical records of 88 consecutive patients (110 eyes) with DME. These patients received at least one intravitreal injection of bevacizumab. Sixteen eyes (14.5 percent) needed a second injection, and six eyes (5.7 percent) needed a third injection.

They found that the anatomical and visual benefit of the intravitreal bevacizumab reached its maximum value during the first month and then maintained that value over six months.

While these results appear promising, it is too early to make treatment recommendations. The authors call for a controlled clinical trial with longer follow-up to evaluate the safety and efficacy of this treatment approach.

AMD Associated With Incident Myocardial Infarction in Elderly Americans
April?€™s Ophthalmology

Findings from a cross-sectional investigation by Duan et al. indicate that AMD is associated with a history of myocardial infarction (MI) when compared with patients who do not have AMD.

Additionally, in a prospective analysis of their data, baseline AMD is significantly associated with the development of incident MI, and this link between AMD and MI is stronger for neovascular AMD.

The authors studied a 5 percent random sample of Medicare enrollees from 2000 to 2003. Occurrence of AMD was associated with older age, female gender and being white. Baseline age-, gender- and race-adjusted prevalence of hypertension, diabetes and MI history were 75 percent, 33 percent and 5 percent, respectively, in the neovascular AMD group, compared with 73 percent, 27 percent and 4.68 percent in the non-neovascular AMD group, and 65 percent, 25 percent and 4.54 percent in the non-AMD group.

If these findings are confirmed by additional studies that control for smoking and other lifestyle covariables, there may be a possibility of shared common antecedents between MI and AMD.

American Journal of Ophthalmology

Retinal Pigment Epithelial Transplantation in AMD
April?€™s AJO

Tezel et al. evaluated the use of retinal pigment epithelial (RPE) cell transplantation and systemic immunosuppression at the time of surgical removal of subfoveal choroidal neovascularization in exudative AMD in order to improve visual function.

The authors hypothesized that repopulation of host Bruch?€™s membrane by transplanted RPE may avoid secondary atrophy of the subfoveal choriocapillaris and lead to visual recovery of the overlying photoreceptors.

One eye only of each of the 12 patients with exudative AMD underwent subfoveal membranectomy with transplantation of a sheet of adult human allogeneic RPE cells. The patients were followed for one year.

Eligibility criteria included age greater than 60, BCVA of less than 20/63 and subfoveal neovascularization less than 9 disc areas on preoperative fluorescein angiography. All patients were started on triple immunosuppression postoperatively. The primary outcome measure was BCVA with contrast sensitivity and reading speed as secondary measures.

BCVA, contrast sensitivity and reading speed did not change significantly at one year compared with preoperative values. Transplants showed no signs of rejection in patients who were able to continue the immunosuppressants for six months.

Postoperative surgical complications included cataract progression requiring surgery (three of eight phakic eyes), retinal detachment (three eyes), retinal breaks (two eyes) and macular pucker (two eyes). None of the patients developed cystoid macular edema on postoperative fluorescein angiography, or postoperative inflammation.

Although adult human allogeneic RPE can be transplanted into the subretinal space in AMD patients at the time of subfoveal membranectomy without evident rejection, it did not lead to an improvement in visual function.

OCT-Guided Intravitreal Ranibizumab for Neovascular AMD
April?€™s AJO

Fung et al. evaluated an OCT-guided, variable-dosing regimen with intravitreal ranibizumab for the treatment of patients with neovascular age-related macular degeneration (AMD) in a prospective, nonrandomized, clinical study over a two-year period.

Patients with subfoveal choroidal neovascularization (CNV) from AMD (n = 40) and a central retinal thickness of at least 300 µm as measured by OCT were enrolled to receive three consecutive, monthly, intravitreal injections of ranibizumab (0.5 mg). Thereafter, re-treatment with ranibizumab was performed if one of the following changes was observed between visits: a loss of five letters in conjunction with fluid in the macula as detected by OCT, an increase in OCT central retinal thickness of at least 100 µm, new-onset classic CNV, new macular hemorrhage, or persistent macular fluid detected by OCT at least one month after the previous injection of ranibizumab.

At month 12, the mean visual acuity improved by 9.3 letters (P < 0.001) and the mean OCT central retinal thickness decreased by 178 µm (P < 0.001). Visual acuity improved 15 or more letters in 35 percent of patients. These visual acuity and OCT outcomes were achieved with an average of 5.6 injections over 12 months. After a fluid-free macula was achieved, the mean injection-free interval was 4.5 months before another reinjection was necessary.

This OCT-guided, variable-dosing regimen with ranibizumab resulted in visual acuity outcomes similar to the phase 3 clinical studies, but required fewer intravitreal injections.

The Macular Automated Photostress Test
April?€™s AJO

Dhalla et al. introduced a standardized macular photostress test using an automated perimeter as a method to quantify macular disease severity and as a tool to distinguish optic neuropathy from macular pathology.

The study patients consisted of 25 bilaterally pseudophakic subjects: 15 patients with varying severity of non-neovascular age-related macular degeneration, five patients with no ocular disease and five patients with moderate primary open-angle glaucoma (POAG). Previously reported normative values served as controls for this study. Patients underwent foveal threshold testing using the Humphrey Visual Field Perimeter Model 750. Baseline measurements were compared to threshold sensitivity after photostress at one-minute and then two-minute intervals until sensitivity returned to baseline. Main outcome measures were baseline foveal threshold sensitivity, foveal threshold depression and recovery following photostress.

Automated macular photostress testing in macular disease (AMD) causes a decrease (P < 0.001) in baseline foveal sensitivity and a delay (P < 0.001) in recovery time to baseline sensitivity. Optic nerve pathology (POAG) does not affect the foveal response curve. This test may be an inexpensive, noninvasive and readily accessible adjunct for evaluating patients with macular disease. This standardized protocol seems useful in objectively defining disease severity, may be used to follow response to treatment and could aid in distinguishing optic neuropathy from macular pathology.

Archives of Ophthalmology

Genotype-Phenotype Correlation in von Hippel-Lindau Disease With Retinal Angiomatosis
February?€™s Archives

In a cross-sectional study, Wong et al. examined a large population of patients with von Hippel-Lindau (VHL) disease to determine the prevalence of ocular involvement with retinal capillary hemangioblastomas (RCHs) and to correlate the genotype of mutations in the VHL gene with the ocular phenotype.

Eight hundred and ninety patients with clinically defined systemic VHL disease had ocular exams including dilated ophthalmoscopy to determine their ocular phenotype. Of these, 834 patients could be classified by germline mutations into one of three genotypic classes, based on the mutational effect on the VHL protein: amino-acid substitutions, protein-truncating mutations, and complete deletion of the VHL protein. Genotype-phenotype correlations were drawn between these genotypic classes and the ocular phenotype of these patients.

Data analysis revealed that the genotype of VHL mutations had a significant effect on ocular VHL disease. The prevalence of ocular involvement with RCHs was significantly lower for complete deletions (14.5 percent) than for either amino-acid substitutions (38 percent) or for protein-truncating mutations (40.1 percent).

Among patients with ocular VHL disease, complete deletions also appear to have less impact on visual function than other mutations. Patients with complete deletions had a mean visual acuity of 84.7 letters (equivalent to visual acuity of 20/20) in the worse- seeing eye, significantly higher than that for either amino-acid substitutions (54.9 letters or 20/80) or protein-truncations (51.7 letters or 20/100).

Genotype category had no discernable effect on the laterality of ocular involvement or the number and extent of peripheral VHL tumors.

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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

Etanercept to Treat Mucous Membrane Pemphigoid
Archives of Dermatology
2006;142:1457?€“1461

Mucous membrane pemphigoid is an autoimmune blistering disorder that can lead to stricture formation of the mucosal surfaces and blindness. According to Canizares et al., effective treatment modalities are often toxic.

Based on two previous reports in the literature, the authors describe a novel therapeutic approach involving subcutaneous injections of 25 mg of etanercept twice weekly. The three participants described had oral mucosal involvement, and one had severe, recalcitrant ocular disease. Within four weeks of treatment, all three patients experienced improvement in oral mucosal disease. The patient with ocular involvement was originally found to have bilateral symblephara, a left conjunctival and corneal ulceration with subepithelial erythema and early fibrosis, and bilateral keratopathy. One year later, after failing 10 cycles of intravenous immunoglobulin, the patient was given subcutaneous injections of 25 mg of etanercept twice weekly. Improvement was seen within four weeks. After two years, she continued to be free from oral, scalp or active ocular involvement, and her symblephara remained stable.

Given these findings, the authors believe a randomized, controlled clinical trial is warranted to further investigate the safety of etanercept and other antitumor necrosis factor alpha agents in the treatment of mucous membrane pemphigoid.

Intraoperative Floppy Iris Syndrome During Cataract Surgery
British Journal of Ophthalmology
2007;91:40?€“42

Chadha et al. assessed if there is an association between intraoperative floppy iris syndrome (IFIS) during cataract surgery and the use of alpha1 antagonists, and diabetes mellitus.

The authors prospectively enrolled 1,842 eyes of 1,786 patients undergoing phacoemulsification surgery, making sure to note the use of alpha1 antagonists and any diabetes diagnoses.

They found that tamsulosin use was associated with IFIS, although in varying severity: 43 percent of patients on tamsulosin did not have any IFIS features.

While the authors cannot explain this continuum of severity in patients on tamsulosin, they speculate that therapy duration, dose, individual susceptibility to the drug, drug kinetics and coexisting ocular and systemic factors may all have some role in determining which patients will be affected.

In contrast, doxazosin was not associated with the syndrome, nor did the authors find an association between diabetes and IFIS.

The authors conclude with a caveat that not all patients on tamsulosin will experience IFIS and not all IFIS cases will necessarily be in patients on tamsulosin.

Retinal Toxicity Not Found in Rabbit Eyes Injected With Kenalog
Investigative Ophthalmology & Visual Science
2007;48:390?€“395

Albini et al. conducted a study to determine whether intravitreal Kenalog (IVTK) delivered at a concentration 2.6 times that of routine clinical IVTK caused functional or structural deleterious effects during a 12-week period (five half-lives of triamcinolone acetonide).

One eye of the rabbits was injected with 4 mg/0.1 ml Kenalog, and 0.1 ml physiologic salt solution (PSS) was injected in the fellow eye. The researchers assessed function by electroretinography and structure problems by macroscopy, histopathology and immunohistochemistry. At two and 12 weeks after injection, electroretinography showed no statistically significant difference between the IVTK-injected eyes and PSS-control eyes. Light microscopy and immunohistochemistry showed only rare macrophages in the vitreous of IVTK-injected eyes.

In addition, no differences in the retinal layers, retinal pigment epithe-lium and choriocapillaris could be detected in the treatment and control eyes.

The investigators conclude that toxicity studies performed in higher animals may be more reliably extrapolated to humans.

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

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More Online Access

In addition to Ophthalmology, Academy members now have free online access to the American Journal of Ophthalmology, Survey of Ophthalmology and Ophthalmology Clinics of North America.  See Academy Notebook for more details.