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March 2006

Journal Highlights

New Findings from Ophthalmology, AJO and Archives

April’s Ophthalmology:
• Immune Recovery Uveitis Substantial in Patients With AIDS and CMV Retinitis
• Posterior Capsular Tear Increases Risk of Retinal Detachment Following Cataract Surgery
• Ranibizumab Safe, Associated With Improved Visual Acuity in Neovascular AMD
• Infectious Keratitis Very Rare Complication Following PRK

March’s American Journal of Ophthalmology:
• Enoxaparin Minimizes Inflammatory Reaction After Pediatric Cataract Surgery
• Diabetic Retinopathy in a Multiethnic Cohort in the United States
• Effect of Optic Material and Haptic Design on ACO and Capsulorhexis Contraction

 Archives of Ophthalmology:
• Quality of Life After Iodine-125 Brachytherapy vs. Enucleation for Choroidal Melanoma
• Age-Related Eye Disease, Visual Impairment and Survival: The Beaver Dam Eye Study
• Iris Pigment Epithelial Translocation for Exudative Macular Degeneration

Roundup of Other Journals:
• SolarScan for Diagnosis of Primary Melanoma
• Early Complications of Deep Lamellar Endothelial Keratoplasty
• Surgical Monovision With LASIK for Presbyopia


Immune Recovery Uveitis Substantial in Patients With AIDS and CMV Retinitis
April’s issue

The availability of highly active antiretroviral therapy (HAART) has ushered in a new era for patients with HIV disease, improving the prognosis of cytomegalovirus retinitis in patients on this regimen. However, patients with HAART-immune recovery are at risk for another problem, immune recovery uveitis (IRU), an ocular inflammatory syndrome.

In a 19-clinical-center cohort study involving 374 patients with AIDS and CMV retinitis affecting 539 eyes, Kempen et al. found that their risk of developing IRU was substantial. In addition, eyes with IRU had significant associated morbidity, with a greater than 20-fold higher risk of cystoid macular edema, and about five- to sixfold higher risk of epiretinal membrane than eyes without IRU. Risk factors for IRU included large CMV lesion size and the use of intravitreal cidofovir.

The authors call for further research to determine whether IRU can be prevented and to improve its treatment.

Posterior Capsular Tear Increases Risk of Retinal Detachment Following Cataract Surgery
April’s issue

In a case-controlled study of 249 eyes that developed rhegmatogenous retinal detachment following cataract extraction, Tuft et al. found that a posterior capsular tear increases the risk of detachment by approximately 20 times compared with uncomplicated surgery. To determine risk factors for rhegmatogenous retinal detachment after cataract surgery, a consecutive series of 63,298 cataract surgery procedures in 45,520 patients was identified.

Researchers matched 249 cases of pseudophakic retinal detachment with 845 controls who had cataract surgery on the same day but no detachment. In addition to posterior capsular tears, other risk factors for retinal detachment included zonular dehiscence, retinal detachment in the fellow eye, axial length greater than 23 millimeters, and male gender.

In contrast, factors such as surgical technique, type of anesthesia, prior glaucoma, or subsequent Nd:YAG laser posterior capsulotomy were not significantly related to retinal detachment.

Ranibizumab Safe, Associated With Improved Visual Acuity in Neovascular AMD
April’s issue

Heier et al. have found that treatment involving repeated intravitreal injections of anti-VEGF ranibizumab (Lucentis) has a good safety profile and is associated with improved visual acuity and decreased leakage from choroidal neovascularization in patients with neovascular AMD.

The six-month phase 1/2, controlled, multicenter, multidose study involved 64 patients with AMD-related CNV randomized to monthly intravitreal ranibizumab for three months or to standard care. In the second phase of the trial, participants could continue their regimen for three additional months or choose the alternative treatment.

The most common adverse effects were reversible inflammation and minor injection-site hemorrhages. Three patients had more serious problems. One patient experienced iridocyclitis, another endophthalmitis and a third central retinal vein occlusion. Improvement in visual acuity occurred rapidly following the first ranibizumab injection and continued to improve gradually between days 14 and 98; this benefit persisted between days 98 and 210. Despite the small number of participants in this study and short follow-up period, the authors assert their research provides encouraging preliminary support for the use of anti-VEGF therapy for neovascular AMD.

Infectious Keratitis Very Rare Complication Following PRK
April's issue

A retrospective review by Wroblewski et al. of the incidence of infectious keratitis following photorefractive keratectomy at six Army and Navy refractive surgery centers has shown that this condition is rare and appears early in the postoperative period.

Of the 25,337 PRK procedures performed from January 1995 to May 2004, culture-proven or clinically suspected infectious keratitis was identified in five eyes of five patients. The condition presented two to seven days following surgery in all cases. Despite the use of prophylactic fluoroquinolones, and trimethoprim-polymyxin B in one patient, cultures from four cases grew Staphylococcus, including two cases of methicillin-resistant Staphylococcus aureus. Four of the patients received topical fluoroquinolones until the corneal epithelium healed; the fifth patient received trimethoprim-polymyxin B.

The authors suggest that preoperative antibiotics may be helpful in preventing this complication.


Enoxaparin Minimizes Inflammatory Reaction After Pediatric Cataract Surgery
American Journal of Ophthalmology
March’s issue

Pediatric cataract surgery is occasionally accompanied by marked intraocular inflammation. Rumelt et al. evaluated the effect of an intraoperative, intraocular infusion of enoxaparin, a low-molecular-weight heparin, on postoperative inflammatory response in pediatric cataract surgery in a prospective, comparative, consecutive interventional case series.

Seventeen consecutive eyes (11 patients) underwent pediatric cataract surgery using balanced salt solution with enoxaparin (40 milligrams in 500 milliliters) infused into the anterior chamber. Eleven consecutive control eyes (eight patients) received balanced salt solution without enoxaparin in the infusion bottle.

The inflammatory response in the anterior chambers of patients in the two groups was compared by semiquantification with slit-lamp biomicroscopy. Postoperative inflammatory complications, including fibrin formation, IOL precipitates, anterior and posterior synechiae, cyclitic and pupillary membrane formation, and anterior subluxation of the IOLs were also compared. The follow-up period after surgery was between three and 36 months.

The number of cells and the degree of flare were minimal in the group with enoxaparin in the infusion bottle (P < 0.001). The total number of postoperative inflammation-related complications was also lower in the enoxaparin-treated group (P = 0.007). The endothelial cell count, which was performed in two patients, did not show substantial decrease in their density or changes in shape and size. No other enoxaparin-related complications were observed. Infusion of enoxaparin during pediatric cataract surgery may minimize the postoperative inflammatory response and decrease the number of postoperative inflammatory-related complications. Enoxaparin might be considered especially when cataract surgery is being performed in certain situations anticipating a postsurgical inflammatory state.

Diabetic Retinopathy in a Multiethnic Cohort in the United States
American Journal of Ophthalmology
March's Issue

Many diseases have distinct patterns of behavior or progression among different ethic groups. Wong et al. from the Multi-Ethnic Study of Atherosclerosis (MESA) group described the prevalence and risk factors of diabetic retinopathy in a multiethnic U.S. population of whites, blacks, Hispanics and Chinese with a cross-sectional study of 778 individuals, aged 45 to 85 years, with diabetes.

Retinal photographs were obtained with a 45-degree nonmydriatic digital fundus camera. Presence and severity of diabetic retinopathy were graded at a central reading center on the basis of a modification of the Airlie House classification system. All participants underwent a standardized interview, examination and laboratory investigation.

In this population, the prevalence of any retinopathy was 33.2 percent and macular edema 9 percent. The prevalence of any diabetic retinopathy and macular edema was significantly higher in blacks (36.7 percent and 11.1 percent, respectively) and Hispanics (37.4 percent and 10.7 percent) than in whites (24.8 percent and 2.7 percent) and Chinese (25.7 percent and 8.9 percent) (P = 0.01 and P = 0.007, comparing racial/ethnic differences for retinopathy and macular edema, respectively). Significant independent predictors of any retinopathy were longer duration of diabetes, higher fasting serum glucose, use of diabetic oral medication or insulin, and greater waist-hip ratio. Race was not an independent predictor of any retinopathy.

Effect of Optic Material and Haptic Design on ACO and Capsulorhexis Contraction
American Journal of Ophthalmology
March’s issue

There is ongoing debate on the influence of IOL properties on subsequent need for additional postcataract surgery. Sacu et al. examined the influence of the optic material (silicone and hydrophobic acrylic) and the haptic design (one-piece and three-piece) of sharp-optic-edged IOLs on anterior capsular opacification (ACO) and capsulorhexis contraction. The researchers conducted a randomized, controlled, double-blind trial with intraindividual comparison.

The study comprised 210 eyes of 105 patients with bilateral age-related cataract. In group 1 (n = 53 patients), a three-piece acrylic IOL was compared with a three-piece silicone IOL. In group 2 (n = 52 patients), the three-piece acrylic IOL was compared with the one-piece acrylic IOL. One year after the operation, standardized digital slit-lamp images of ACO were taken; one week and one year after the operation, digital retroillumination images were taken to assess capsulorhexis size. The intensity of ACO was graded objectively (score, 0 percent to 100 percent) and the capsulorhexis area (square millimeters) was determined objectively.

One year after surgery, the mean ACO score in group 1 was 21 percent for the acrylic and 20 percent for the silicone IOL (P = 0.4). In group 2, it was 18 percent for both the three-piece and one-piece acrylic IOLs (P = 0.87). There was no significant difference between the IOL types in the amount of capsulorhexis contraction.

The authors conclude that, in the hydrophobic sharp-optic-edged IOLs that were examined, neither the optic material nor the haptic design had an influence on the amount of ACO or capsulorhexis contraction.

Quality of Life After Iodine-125 Brachytherapy vs. Enucleation for Choroidal Melanoma
Archives of Ophthalmology
February’s issue

This study described health- and vision-targeted quality of life following treatment with I125 brachytherapy vs. enucleation for choroidal melanoma.

Two hundred nine patients who enrolled in the Collaborative Ocular Melanoma Study trial for medium-sized tumors participated in this ancillary study of quality of life and were randomly assigned to treatment with I125 brachytherapy or enucleation. Patients were interviewed by telephone using a battery of standard quality-of-life questions prior to study randomization, again at six months, and on annual anniversaries of study enrollment.

There was a significant increase in both treatment groups in levels of reported difficulty for most vision-oriented activities, and in bodily and ocular pain, at six months following treatment. Differences in visual function between treatment groups were relatively small, but at one year follow-up brachytherapy patients reported fewer problems with driving than those in the enucleation group. And at two years, they reported fewer problems with peripheral vision than did the enucleation patients.

Anxiety levels in both the groups decreased significantly following treatment, but patients treated with brachytherapy with symptoms of anxiety were less likely to report later resolution of those symptoms than patients who were treated with enucleation. No treatment-related differences were found at two years or later follow-up times.

Given that no significant differences in survival between enucleation and brachytherapy were found, patients and physicians can make treatment choices based on a patient’s preferences.

Age-Related Eye Disease, Visual Impairment and Survival: The Beaver Dam Eye Study
Archives of Ophthalmology
February’s Issue

Knudtson et al. investigated the long-term relationship of age-related maculopathy, cataract, glaucoma, visual impairment and diabetic retinopathy to survival over a 14-year period.

Persons ranging in age from 43 to 84 years from 1987 to 1988 participated in the baseline examination of the population-based Beaver Dam Eye Study (n = 4,926). Standardized protocols, including photography, were used to determine the presence of ocular disease. Survival was followed using standardized protocols.

As of Dec. 31, 2002, 32 percent of the baseline population had died (median follow-up of 13.2 years). After adjusting for age, gender, systemic and lifestyle factors, poorer survival was associated with cortical cataract (hazard ratio [HR] 95 percent confidence interval [CI]: 1.21 (1.06,1.37)), any cataract (HR, CI: 1.16 (1.03,1.32)), diabetic retinopathy (HR, CI: 1.36 (1.14,1.63) per 1-step increase in 4-level severity), and visual impairment (HR, CI: 1.24 (1.04,1.48)). Poor survival was marginally associated with increasing severity of nuclear sclerosis (HR, CI: 1.07 (0.99, 1.16)). Age-related maculopathy and glaucoma were not associated with poorer survival. Associations tended to be slightly stronger in men than in women.

The authors conclude that cataract, diabetic retinopathy and visual impairment were associated with poorer survival and not explained by traditional risk factors for mortality. These ocular conditions may serve as markers for mortality in the general population.

Iris Pigment Epithelial Translocation for Exudative Macular Degeneration
Archives of Ophthalmology
February’s Issue

Aisenbrey et al. examined the long-term effect of subretinal transplantation of iris pigment epithelium (IPE) cell suspensions in age-related macular degeneration patients.

Autologous IPE cells were translocated to the subretinal space in 20 consecutive patients aged 33 to 85 years with subfoveal choroidal neovascularization. Nine patients had classic CNV secondary to AMD, seven patients had occult CNV secondary to AMD, two patients had idiopathic CNV, one patient had a CNV secondary to high myopia, and one patient had a CNV secondary to dominant drusen.

After three-port pars plana vitrectomy and extraction of the CNV, freshly isolated IPE cells in suspension were injected into the subretinal space.

A large iridectomy was performed through a peripheral corneal incision on the eyes undergoing vitrectomy. The tissue was placed in a glass well with a drop of balanced salt solution, and the IPE cells were mechanically isolated from the underlying stroma without enzymes. For injection, the cells were suspended in 20 microliters of BSS.

The site of translocation was evaluated by funduscopy and fluorescein angiography. Fixation behavior was tested by scanning laser ophthalmoscopic (SLO) microperimetry. Visual acuity was measured with Early Treatment Diabetic Retinopathy Study (ETDRS) charts at defined time intervals.

Seventeen patients were followed for a period of at least three years after IPE translocation. At three years, one patient showed improved visual acuity of more than two ETDRS lines, 13 patients retained stable visual acuity, and three patients had reduced visual acuity of more than two ETDRS lines compared with their preoperative visual acuity. SLO examination showed that central fixation was not regained or preserved in any of the patients. No macular edema or recurrent CNV was apparent by fluorescein angiography at any time during the three-year follow-up.

The authors conclude that autologous IPE cells transplanted to the subretinal space are well tolerated for three years and do not adversely affect photoreceptor function. However, visual function is not improved beyond what would be expected by membrane removal alone. CNV did not recur in any of these patients, suggesting that the value of IPE transplantation may be in preventing CNV recurrence following CNV removal in AMD patients.

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

SolarScan for Diagnosis of Primary Melanoma
Archives of Dermatology
2005;141:1388–1396, 1444–1446 (editorial)

In a nine-center study covering three continents, Menzies et al. have found that SolarScan (Polartechnics Ltd.) shows promising results as an automated tool to diagnose primary melanoma. The study involved images from a data set of 2,430 pigmented skin lesions, in which 382 were melanomas with a median Breslow thickness of 0.36 millimeters.

These lesions were divided into a training set and an independent test set; high-quality clinical and dermascopy images with a detailed patient history for 78 lesions from the test set were given to various clinicians to compare their diagnostic accuracy with that of SolarScan.

SolarScan had comparable or superior sensitivity and specificity compared with those of experts, dermatologists, trainees and general practitioners. The researchers caution that this technology will never be 100 percent accurate.

Also an accompanying editorial by Rubegni et al. warns that all digital systems have inherent limits, “particularly automated systems designed to provide a clinical decision.” Consequently, these sophisticated instruments should only be used by experienced dermatologists.

Early Complications of Deep Lamellar Endothelial Keratoplasty

Results looking at early complications of deep lamellar endothelial keratoplasty (DLEK) show that complications from the surgery are relatively rare and easily resolved, but the authors warn that because it is so technically challenging surgeons must be highly proficient in the technique to obtain low complication rates.

The prospective study by Terry and Ousley involved the first 100 consecutive DLEK cases performed by a single surgeon. Of the 98 patients who had completed DLEK surgery (two were converted to penetrating keratoplasty), four experienced a dislocated disk on the first postoperative day, a problem resolved by repositioning the disk. One eye had primary graft failure caused by surgeon error, resulting in a disk dislocation that was successfully replaced with another disk the day after surgery. Four patients experienced graft rejection after stopping steroids, but all grafts cleared upon resumption of steroids. Additionally, there were no infections, ulcerations, healing defects or late dislocations.

The authors conclude that DLEK represents a viable alternative to standard penetrating keratoplasty surgery, and it eliminates need for sutures and provides a considerable “safety margin” not found in other forms of endothelial replacement surgery. However, they caution that surgeons should undergo extensive training with animal and cadaver models before attempting DLEK.

Surgical Monovision With LASIK for Presbyopia

Monovision represents a workable alternative for presbyopia in contact lens wearers, with success rates between 50 percent and 75 percent. Yet is this treatment strategy successful in LASIK patients?

A study by Reilly et al. indicates that surgical monovision can, in fact, help presbyopic patients reduce their dependence on glasses. The researchers analyzed 82 patients who underwent LASIK for monovision; 97 percent achieved success defined as those patients who elected not to have their monovision reversed and who had J2 near vision or better. None of the patients who underwent a contact lens trial of monovision prior to LASIK elected monovision reversal, whereas two patients who did not undergo this contact lens trial chose monovision reversal.

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