EyeNet Magazine


 
Journal Highlights

New Findings from Ophthalmology, AJO and Archives
 
 

May’s Ophthalmology:

Subcutaneous Daclizumab for Noninfectious Uveitis Shows Promising Early Results

Diabetes Mellitus, Not Systemic Hypertension, Is a Significant Risk Factor for Sixth Nerve Palsy

25-Gauge Transconjunctival Surgery vs. Pars Plana Vitrectomy

A High Incidence of Age-Related Maculopathy Is Found in an Elderly White Population

Intralesional Triamcinolone Acetonide Injections for Chalazia

April’s American Journal of Ophthalmology:

Expression of Angiopoietins and VEGF in Subfoveal Membranes From AMD Patients

A Telemedicine Program for Diabetic Retinopathy

Polyacrylic IOLs and Posterior Capsular Opacification

Effect of Sharp Posterior Optic Edge of Silicone IOL on Capsular Opacification

March’s Archives of Ophthalmology:

Results From a Multicenter Trial of Cryotherapy: 15-Year Outcomes Following Threshold ROP

Trends in the Microbiology of Post-Cataract Endophthalmitis

Perceived Barriers to Diabetic Eye Care: A Qualitative Study of Patients and Physicians

Tadalafil Associated With AION

Round of Other Journals:

Novel Adult-Onset Primary Open-Angle Glaucoma Gene Is Identified

TGFß Mutations Cause Marfan-Like Syndrome

Disability at 6 Years After Extremely Preterm Birth

Previews

Subcutaneous Daclizumab for Noninfectious Uveitis Shows Promising Early Results
Ophthalmology
May’s issue

Nussenblatt et al. have found that subcutaneous administration of the interleukin-2 receptor antibody daclizumab every two weeks for up to six months can safely reduce corticosteroid or other systemic regimens previously required to control noninfectious uveitis.

This case series involved 15 patients who required systemic corticosteroids and/or other systemic treatments to control intraocular inflammation. They received two induction treatments two weeks apart of subcutaneous daclizumab (2 milligrams per kilogram). Maintenance treatments were continued every two weeks at 1 mg/kg for six months. The initial immunosuppression load was tapered over eight to 12 weeks beginning with the first induction treatment.

Results showed that 10 of the 15 patients reduced their concomitant immunosuppression load by at least 50 percent while maintaining their baseline visual acuity at 12 and 26 weeks. These injections were well-tolerated with no serious adverse events.

The authors conclude that the convenience and safety of subcutaneous daclizumab may make it commercially viable. However, well-controlled trials are required to develop adequate safety and efficacy data.

Diabetes Mellitus, Not Systemic Hypertension, Is a Significant Risk Factor for Sixth Nerve Palsy
Ophthalmology
May’s issue

Results from a population-based study by Patel et al. confirm the widely held belief that diabetes mellitus is an independent risk factor for sixth nerve palsy—a common cause of diplopia.

However, contrary to popular belief, hypertension may not be a risk factor for this condition. The investigators identified the records of potential cases and controls from the Rochester Epidemiology Project conducted in Olmsted County, Minn. Seventy-six identified patients who had new onset of neurologically isolated sixth nerve palsy and controls were matched for age, sex and length of medical follow-up.

A sixfold increase in odds of having diabetes was found in patients with sixth nerve palsy as compared with controls. While systemic hypertension did not appear to be associated with increased prevalence, there was an eightfold increased odds of having coexistent diabetes and hypertension in those individuals with sixth nerve palsy.

The authors conclude that hypertension alone should not be considered the sole cause of neurologically isolated sixth nerve palsy.

25-Gauge Transconjunctival Surgery vs. Pars Plana Vitrectomy
Ophthalmology
May’s issue

Lakhanpal et al. have found that under optimal conditions, 25-gauge transconjunctival surgical procedures may prove a safe and effective alternative to traditional conventional pars plana vitrectomy for a variety of posterior segment conditions, including idiopathic epiretinal membrane, choroidal neovascular membrane, nonclearing vitreous hemorrhage and macular hole.

The authors evaluated 140 eyes of 140 patients who underwent surgical procedures with the 25-gauge system. No cases required conversion to 20-gauge machines, and 10 cases involved single-site sclerotomy suture placement due to bleb formation at the conclusion of the procedure. The authors cited several potential advantages of 25-gauge instrumentation over 20-gauge pars plana vitrectomy, including elimination of nonessential steps; ability to perform certain procedures without sutures, in less overall time and with less postoperative inflammation; reduction of actual surgical time; and less traumatic external appearance in the immediate postoperative period.

They also noted that case selection was key to success, concluding that the 25-gauge approach may be better suited for procedures requiring minimal intraocular manipulation.

A High Incidence of Age-Related Maculopathy Is Found in an Elderly White Population
Ophthalmology
May’s issue

Findings from a 14-year population-based study of 359 Caucasian Copenhagen residents aged 60 to 80 at baseline indicate a high incidence of age-related maculopathy lesions. Buch et al. also found that severe drusen type and size or retinal pigmentary abnormalities significantly increased the risk of developing late ARM.

The study, which began in 1986, showed 14-year incidences of early and late ARM at 31.5 percent and 14.8 percent respectively. Severe drusen type, large drusen and retinal pigmentary abnormalities at baseline were key predictors of incident late ARM. The strength of this study was that it occurred before the availability of antioxidant prevention therapy for ARM. Also, the percentage of participants with incident late ARM who had received laser or photodynamic therapy treatment was less than 5 percent—providing a unique opportunity to study the natural course of ARM.

The study confirmed the importance of drusen and pigmentary abnormalities as an important risk factor for developing late ARM; these patients could possibly benefit from preventive strategies.

Intralesional Triamcinolone Acetonide Injections for Chalazia
Ophthalmology
May’s issue

Ben Simon et al. report that intralesional triamcinolone acetonide may be effective as a first-line treatment alternative in straightforward cases of primary and recurrent chalazia, a common eyelid disease caused by plugged meibomian glands and chronic lipogranulomatous inflammation.

In a retrospective consecutive case series of 147 patients (155 cases) treated with an intralesional injection of 0.1 to 0.2 milliliters of triamcinolone acetonide (40 milligrams/ml), resolution of the condition was achieved after an average of 2.5 weeks in more than 80 percent of patients. A single injection was sufficient in more than half of the patients, and these individuals demonstrated an even faster response. No complications such as visual loss, subcutaneous fat atrophy or skin depigmentation changes were noted.

The authors conclude that injections of intralesional triamcinolone acetonide are safe and effective in treating primary and recurrent chalazia. However, if individuals fail to respond after a third injection, surgical excision may be the next logical step.

Reviews

Expression of Angiopoietins and VEGF in Subfoveal Membranes From AMD Patients
American Journal of Ophthalmology
2005:139:589–596

Angiopoietins and vascular endothelial growth factor are key regulators of angiogenesis in the retina and elsewhere.

Hera et al. measured mRNA levels of these factors and of their receptors in a prospective observational case series of surgically excised subfoveal membranes from patients with age-related macular degeneration. They also evaluated their relevance as prognostic markers of postsurgical recurrence of CNV.

Subfoveal membranes from 24 eyes of 24 patients with classic CNV of AMD diagnosed less than six months previously were surgically removed and collected. Thirteen patients underwent treatment for recurrence of CNV within six months of surgery. Two 8-micrometer sections were prepared from each membrane for immunohistochemical determination of vascular density. The remaining tissue was used for preparation of total RNA. The levels of VEGF-A, VEGF-R1, VEGF-R2, neuropilin-1, angiopoietin-1, angiopoietin-2, Tie-2 and hypoxanthine phosphoribosyltransferase mRNAs were determined by real-time reverse transcriptase polymerase chain reaction.

Vascular endothelial growth factor, angiopoietin-1 and angiopoietin-2 appeared to be expressed to variable levels in most samples, whereas Tie-2, VEGF-R1 and VEGF-R2 were undetectable. Low levels of VEGF expression correlated with postsurgical recurrence of CNV whereas angiopoietin-1 and angiopoietin-2 levels did not predict recurrence.

At the time of surgical excision, subfoveal membranes express angiopoietin-1, VEGF and, to a lesser degree, angiopoietin-2. Because CNV appears to recur less often in membranes expressing high levels of VEGF, the authors hypothesize that VEGF acts as a stabilizer of neovessels at this stage of the disease.

A Telemedicine Program for Diabetic Retinopathy
American Journal of Ophthalmology
2005:139:597–604

Telemedicine is being actively explored in many venues. In a retrospective observational cohort study, Cavallerano et al. used the Joslin Vision Network telemedicine system to extend access to diabetic eye care and characterize the extent of diabetic eye disease and other ocular findings.

The study involved outpatients at a VA Medical Center with diabetes mellitus, impaired fasting glucose or impaired glucose tolerance. They were imaged before scheduled nonophthalmic appointments or based on ophthalmic history. JVN–protocol retinal images were transmitted to the Joslin Clinic for grading and recommended treatment plan. Patients with significant diabetic eye disease, with nondiabetic ocular findings or who were overdue for ocular examination were referred for ophthalmic care.

The study included 1,219 patients (2,437 eyes). Of these, 63 percent had no diabetic retinopathy, 16 percent had mild nonproliferative diabetic retinopathy, 4.3 percent had moderate NPDR, 1.4 percent had severe NPDR, 0.8 percent had very severe NPDR and 0.9 percent had proliferative diabetic retinopathy.

With regard to diabetic macular edema, 78.3 percent had no DME, 1.4 percent had early DME and 0.7 percent had clinically significant macular edema.

Of the total sample, 29 percent had either no diabetic retinopathy or mild NPDR in both eyes, no evidence of DME and no significant nondiabetic findings; 55.7 percent of patients had no diabetic retinopathy in either eye; and 18.8 percent had mild NPDR in the more severe eye. Of the 74.5 percent with either no diabetic retinopathy or mild NPDR in the more severe eye, 58.7 percent had at least one nondiabetic ocular finding necessitating referral. Some eyes (13.1 percent) were ungradable for level of both diabetic retinopathy and DME, and other eyes (6.6 percent) were ungradable for DME alone.

In a nonophthalmic setting, JVN identified the severity of diabetic retinopathy and nondiabetic ocular conditions, permitting appropriate triage for eye care. The full potential of this system requires further evaluation.

Polyacrylic IOLs and Posterior Capsular Opacification
American Journal of Ophthalmology
2005:139:691–695

The factors associated with the design of IOLs and opacificaion of the posterior capsule continue to be explored.

Wren et al. performed a retrospective analysis of a cohort of sequential images taken from the posterior capsular opacification database at their hospital. The study included all patients with a 5.5-millimeter polyacrylic (AcrySof MA30) lens that had a one-year retroillumination image.

Records of age, gender, axial length and PCO measurements using the POCO (posterior capsular opacity) software system were available. Images were divided into those with greater or less than 10 percent PCO. The degree of rhexis-IOL contact was recorded in clock hours.

Images of 60 eyes were analyzed. Twenty-one eyes had more than 10 percent PCO. No correlation was found between PCO and age, gender or axial length. Forty-eight eyes (80 percent) had some loss of rhexis-IOL contact. These eyes had increased PCO (P < 0.001) compared with eyes with complete IOL-rhexis contact. More PCO developed when the rhexis was partly on and partly off the IOL.

PCO is reduced when the rhexis is in complete contact with the anterior IOL surface. PCO formation is related to surgical technique as well as IOL design, and comparisons cannot be made between IOLs without taking this into consideration. These results support the trend toward the usage of larger optic IOLs to prevent PCO and also support the “capsule compression” theory of PCO prevention.

Effect of Sharp Posterior Optic Edge of Silicone IOL on Capsular Opacification
American Journal of Ophthalmology
2005:139:696–703

Sacu et al. compared the density of capsular opacification between those eyes that received the sharp optic edge–variant of an open-loop three-piece hydrophobic silicone IOL with those that received the round optic edge–variant.

Fifty-one patients with bilateral age-related cataract (102 eyes) were included in a randomized, controlled, double-blind clinical trial with intraindividual comparison. Each patient had cataract surgery in both eyes and received a Microsil IOL with a sharp optic edge design (model S) in one eye and a Microsil IOL with a round optic edge design (model R) in the fellow eye. Both IOLs had an identical haptic design (nonangulated PMMA) and silicone optic material.

The patients were examined at the slit lamp, BCVA was assessed and standardized high-resolution digital retroillumination images of the posterior capsule were taken five years after surgery.

The intensity of regeneratory PCO, fibrotic PCO and anterior capsular opacification was assessed subjectively at the slit lamp. The intensity of regeneratory PCO also was assessed objectively using automated image analysis software (AQUA). The need for an Nd:YAG laser capsulotomy was noted.

The mean AQUA PCO score was 1.2 for the model S and 2.4 for the model R lens (P = 0.001). The model S lens also led to less peripheral fibrotic PCO (P = 0.003). Concerning anterior capsular opacification, there was no significant difference between both IOL groups (P = 0.72). No capsulotomy was required with the model S, whereas four cases (16 percent) had been performed in the model R group.

Five years postoperatively, the sharp-edged silicone IOL showed less regeneratory PCO and fibrotic PCO than the round-edged IOL. However, regarding anterior capsular opacification, there was no significant difference between the IOL styles.

Results From a Multicenter Trial of Cryotherapy: 15-Year Outcomes Following Threshold ROP
Archives of Ophthalmology
2005:123:311–320

The Cryotherapy for Retinopathy of Prematurity Cooperative Group report on a multicenter randomized trial of cryotherapy for retinopathy of prematurity.

Of  291 preterm children with birth weights less than 1,251 grams and severe (threshold) ROP in one or both eyes, there were 254 survivors at age 15 who participated in this trial.

Examination showed 30 percent of treated eyes, as compared with 51.9 percent of control eyes (P < 0.00001), had unfavorable structural outcomes (i.e., posterior retinal fold, macular detachment or worse). Unfavorable visual acuity outcomes (20/200 or worse) were found in 44.7 percent of treated and 64.3 percent of control eyes (P < 0.00001), yet 12 treated eyes and 18 control eyes had visual acuity of 20/20 or better. 

Between 10 and 15 years, new retinal folds, detachments or obscuring of the view of the posterior pole occurred in 4.5 percent of treated eyes and 7.7 percent of control eyes. 

Thus, the benefits of cryotherapy for threshold ROP were maintained well into the second decade of life. Newly occurring retinal detachments, even in eyes that had had relatively good structural findings at 10 years, suggest value in long-term, regular follow-up of patients with a history of such severe ROP. 

Trends in the Microbiology of Post-Cataract Endophthalmitis
Archives of Ophthalmology
2005:123:341–348

Recchia et al. studied the microbiologic results of 497 consecutive cases of endophthalmitis following cataract surgery.

The eyes were treated at Wills Eye Hospital over an 11-year period. Culture results and in vitro antibiotic susceptibilities were compared between the early and latter halves of the study period.

There was a significant increase in gram-positive isolates (95 percent in the latter period), and an increase in resistance among these isolates to ciprofloxacin, ofloxacin and cefazolin. Resistance of gram-positive bacteria to trimethoprim, bacitracin and vancomycin was statistically unchanged. Vancomycin was effective against more than 99 percent of gram-positive isolates, and ceftazidime was effective against 100 percent of gram-negative isolates tested.

In summary, intravitreal vancomycin and ceftazidime remain effective empiric therapy for endophthalmitis following cataract surgery. However, resistance has grown to certain fluoroquinolones commonly used for endophthalmitis.

Perceived Barriers to Diabetic Eye Care: A Qualitative Study of Patients and Physicians
Archives of Ophthalmology
2005:123:387–391

Harnett et al. studied barriers to diabetic eye care in an indigent care setting in New Orleans. The researchers analyzed responses from structured focus groups of patients and key informant interviews of primary diabetic physicians and ophthalmologists.

While patients said that finance for medications was the major barrier to eye care, physicians cited inadequate patient education. Patients largely believed diabetic education was adequate, yet there was a gap between patient education provided and their understanding of diabetic eye disease and the rationale for eye appointments. No respondent mentioned system capacity constraints as a possible barrier despite a one-year wait for an eye appointment and an increase in eye examinations by 29 percent within two years. 

Several recommendations came from the study: 1) address a patient’s financial barriers because those barriers compound stress associated with the burden of diabetes, 2) develop a one-page synopsis in electronic form to improve communication regarding patient care among physicians, 3) change scheduling and systems to improve access, 4) test the effectiveness of patient education, including the understanding that patients come away with after their physicians’ visits, and 5) enhance communication and education by providing both patients and physicians with a glossary of terms that are commonly used by internists and ophthalmologists.

In summary, this study shows differences in perceptions of barriers to diabetic eye care among physicians and patients. There was a gap in patient understanding of diabetic eye disease despite educational programs. There were also systems difficulties causing poor access and reduced communication among physicians of different disciplines regarding patient care. A large unrecognized workload stresses the capacity of the current system.

Tadalafil Associated With AION
Archives of Ophthalmology
2005:123:399–400

Escaravage et al. report a case study in which a 59-year-old man with prostate cancer underwent an uncomplicated laparoscopic prostatectomy. 

On postoperative day one, he was ambulating and hemodynamically stable when he took 20 milligrams of tadalafil (Cialis). Forty-five hours later he noted sudden “graying” of the inferior visual field of his left eye. Examination six days later revealed inferior altitudinal field loss, a relative afferent pupillary defect and a swollen left optic disc consistent with anterior ischemic optic neuropathy. The left optic disc eventually became pale and the visual field defect did not change.

In summary, this patient experienced AION 45 hours after ingesting tadalafil. It has been shown to be clinically effective until at least 36 hours, the furthest endpoint studied thus far. His only other risk factor for AION was a mild postoperative anemia (hematocrit 25.2 percent).

Roundup of Other Journals

Novel Adult-Onset Primary Open-Angle Glaucoma Gene Is Identified
Human Molecular Genetics
Published online Jan. 27, 2005
DOI: 10.1093/hmg/ddi068
(Go to hmg.oupjournals.org and search by DOI “10.1093/hmg/ddi068”)

Monemi et al. report chromosomal mapping of a new locus for adult-onset primary open-angle glaucoma (POAG)—GLCIG—on the 5q22.1 region and identification of its causative gene, WDR36 (WD40-Repeat 36).

Because WDR36 is a novel gene, the mutation was identified in all affected members of the GLC-IG linked family and not in controls. In addition, three other mutations were identified in 5.02 to 6.92 percent of unrelated POAG families.

WDR36 has recently been identified as one of the genes that is uniquely involved in T cell activation and highly coregulated with interleukin-2. Northern blot analysis revealed two transcripts (5.9-kilobases and 2.5-kb) that were highly expressed in heart, placenta, liver and skeletal muscle.

In addition, the researchers used reverse transcriptase polymerase chain reaction to establish expression of this gene in human ocular tissues (lens, iris, sclera, ciliary muscles, ciliary body, trabecular meshwork, retina and optic nerve) as well as in embryonic and adult mouse tissues. 

The researchers also found that specific ocular expressions and observed mutations were consistent with the WDR36 role in etiology of both high- and low-pressure glaucoma—a key finding that may provide a useful tool for presymptomatic detection of patients at risk.

Since WDR36 has been implicated in the etiology of POAG, the researchers conclude that their discovery provides an opportunity to search for WDR36-interacting proteins, which can lead to the identification of other proteins/ genes that have a direct functional effect on the pathophysiology of POAG.

TGFß Mutations Cause Marfan-Like Syndrome
Natural Genetics
Published online Jan. 30, 2005
DOI: 10.1038/ng1511
(Go to www.nature.com/ng and search for “ng1511”)

The transforming growth factor ßs are a family of multipotential cytokines that influence different cellular fates, including proliferation, migration, synthetic repertoire and death.

Heterozygous TGFßR2 mutations have been previously reported in Marfan syndrome.

While the role of TGFß signaling in developmental and homeostatic processes has been described, there are few examples of genetically defined human pathologic correlates.

In a letter, Loeys et al. present data identifying the vital contribution of TGFß signaling to diverse human phenotypes, including craniosynostosis, cleft palate, arterial aneurysms, congenital heart disease and mental retardation.

Specifically, the researchers described 10 families with TGFßR2 mutations with a new aortic aneurysm syndrome with pathologic findings similar to that seen in patients with Marfan syndrome.

Craniofacial findings included craniosynostosis, proptosis, widely spaced eyes (hypertelorism), exotropia, blue sclera, bifid uvula and/or cleft palate. In addition, generalized arterial tortuosity with ascending aortic aneurysm and dissection was seen.

Their work also demonstrated that isolated consideration of the obvious proximal consequence of a given perturbation may not be enough information to completely understand its mechanisms. Rather, many alterations in the complex processes of TGFß secretion, localization, activation and signaling most likely are required to impact the microenvironments in which morphogenetic events take place.

Disability at 6 Years After Extremely Preterm Birth
The New England Journal of Medicine
2005;352:9–19
(Go to www.nejm.org and select “Past Issues”)

Marlow et al. have observed a high prevalence of disability at early school age (6 years) among children who are born at 25 or fewer completed weeks of gestation.

Of 241 children followed (they were previously evaluated at 30 months), cognitive impairment was the most common disability of the four domains assessed—neuromotor, cognition, hearing and vision—at age 6.

The rates of severe, moderate and mild disability were found to be 22 percent, 24 percent percent and 34 percent, respectively.

Among children with severe disability at 30 months of age, 86 percent still had moderate-to-severe disability at 6 years of age.

In terms of vision problems, four children were blind and two could see only light.

Five of these children had received treatment for retinopathy of prematurity.

Many children had other, less severe visual impairments, including squint (58 children) and the need for eyeglasses (58 children) compared with one control child with a squint and six with refractive errors.

The authors call for further research to determine whether these cognitive impairments may explain the educational difficulties that have been reported for low birth-weight children.




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 is written by Lori Baker Schena and edited by Deepak P. Edward, MD.

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