Review of Ophthalmology Online

Volume 7, Number 46

Monday, November 19, 2007

In this issue: (click heading to view article)

		The Role of Sensory Neuropeptide Substance P in the Pathogenesis of Pterygia

		Cycloplegia for Assessing Refractive Error in 12-Year-Olds

		Mitochondrial DNA Haplogroups and ARM

		Visual Acuity Outcomes After Cataract Extraction in Adult Latinos

		Epidemiological and Genetic Study of X-Linked Retinitis Pigmentosa

		Briefly

The Role of Sensory Neuropeptide Substance P in the Pathogenesis of Pterygia

Pterygium is a prevalent ocular surface disorder thought to be triggered by chronic ultraviolet damage to the limbus. One of the enigmatic features of pterygium is its winglike shape, but the mechanism(s) supporting its centripetal growth have not yet been discovered. Because the growth pattern of pterygia mirrors the radial arrangement of corneal nerves, researchers in this study proposed that neuropeptides may facilitate its directional growth. Their hypothesis prompted an investigation of the role of the sensory neuropeptide substance P (SP) and its receptor, NK(1) receptor, in directing cell migration in pterygia, which may explain the characteristic growth pattern.

The investigators performed immunohistochemical analysis for SP and the NK(1) receptoron five pterygium specimens with corresponding autologous conjunctiva and limbus. Migration of pterygium epithelium, fibroblasts and vascular endothelial cells toward SP was assessed by using a modified Boyden chamber.

SP and NK(1) receptors were localized to infiltrating fibroblasts, mononuclear cells and the epithelia of pterygium, conjunctiva and limbus, with elevated NK(1) receptor staining observed in pterygia. SP at nanomolar concentrations induced cell migration in pterygium fibroblasts and vascular endothelium in a dose-dependent fashion, which was inhibited by an NK(1) receptor antagonist. Pterygium epithelial cells were not migratory in these experiments.

The authors maintain that they have shown for the first time the presence of NK(1) receptor in pterygia and that SP is a potent chemoattractant for pterygium fibroblasts and vascular endothelial cells, implying that SP may contribute to the shape of pterygia through its profibrogenic and angiogenic action.

SOURCE: Chui J, Di Girolamo N, Coroneo MT, Wakefield D. The role of substance P in the pathogenesis of pterygia. Invest Ophthalmol Vis Sci 2007;48(10):4482-9.

Cycloplegia for Assessing Refractive Error in 12-Year-Olds

Using cycloplegic autorefraction in children up to age 12 is an important practice, according to a study by Australia's Centre for Vision Research at the University of Sydney.

The population-based, cross-sectional study of random cluster samples compared pre- and postcycloplegic autorefraction in two separate age samples of Australian school children. Autorefraction was performed before and after cycloplegia, using 1% cyclopentolate, in the right eyes of 2,233 12-year-old and 210 six-year-old children.

The mean spherical equivalent (SEQ) difference between these measures was 0.84 diopters (D) (95 percent confidence interval (CI) 0.81 to 0.87 D), more hyperopic in post- than precycloplegic autorefractive assessments in the 12-year-old children and 1.18 D (95 percent CI 1.05 to 1.30 D) more hyperopic in the six-year-old children. Precycloplegic autorefraction substantially overestimated the proportion of children with myopia, misclassifying 17.8 percent of those aged 12 years, and 9.5 percent of those aged six years. Conversely, precycloplegic autorefraction did not detect moderate-to-high hyperopia in 2.28 percent of 12-year-olds and 17.14 percent of six-year-olds.

SOURCE: Fotedar R, Rochtchina E, Morgan I, et al. Necessity of cycloplegia for assessing refractive error in 12-year-old children: a population-based study. Am J Ophthalmol 2007;144(2):307-9.

Mitochondrial DNA Haplogroups and ARM

This study was aimed at determining whether mitochondrial haplogroups are associated with age-related maculopathy (ARM). Researchers assessed the possible association in a population-based sample of 3,509 people aged 49 years or older residing west of Sydney, Australia. They took retinal photographs of both eyes (1999 to 2001) and subsequently graded for ARM following the Wisconsin grading system. They next performed genetic analysis for mitochondrial DNA haplogroups, and assessed associations between these genetic markers and risk factors for ARM.

After adjusting for age, sex and smoking, haplogroup H was associated with a reduced prevalence of any (early and late) ARM, early ARM and large distinct and indistinct soft drusen. Haplogroup J was associated with a higher prevalence of large, soft distinct drusen. Haplogroup U was associated with an increased prevalence of retinal pigment abnormalities.

The findings of associations between different haplogroup types and prevalent ARM or ARM lesions suggest that these haplogroups may be genetic markers indicating an individual's susceptibility to ARM.

SOURCE: Jones MM, Manwaring N, Wang JJ, et al. Mitochondrial DNA haplogroups and age-related maculopathy. Arch Ophthalmol 2007;125(9):1235-40.

Visual Acuity Outcomes After Cataract Extraction in Adult Latinos

Investigators at Johns Hopkins School of Medicine, Baltimore, conducted this population-based cross-sectional study of adult Latinos to determine prevalence, primary causes and risk indicators of visual impairment in cataract-operated eyes.

The study included 261 participants with cataract extraction. All underwent an in-home interview and a comprehensive ophthalmologic examination. Visual impairment in the cataract-operated eye was defined by presenting visual acuity (PVA) of 20/40 or less or best-corrected visual acuity (BCVA) of 20/40 or less. Investigators evaluated the association of cataract extraction status (aphakic, pseudophakic) and severity of visual impairment, and risk indicators associated with visual impairment by BCVA in the worse-seeing cataract-operated eye.

Of the 261 participants with at least one cataract extraction and a complete clinical examination, 100 participants (38 percent) had undergone a unilateral extraction and 161 (62 percent) had undergone bilateral extractions. The prevalence of visual impairment was 41 percent (107 participants) defined by BCVA and 60.5 percent (158 participants) defined by PVA in the worse-seeing cataract-operated eye, and 32.2 percent (136 participants) defined by BCVA versus 48.1 percent (203 participants) defined by PVA in all cataract-operated eyes. Uncorrected refractive error, age-related macular degeneration and diabetic retinopathy were the primary causes of visual impairment, accounting for 49 percent in worse-seeing cataract-operated eyes and 57 percent in all cataract-operated eyes. Self-reported history of glaucoma, barriers to eyecare and not being married were independent risk indicators associated with visual impairment.

Based on the results of the study, the authors concluded that refractive correction eliminated visual impairment in 15 percent to 20 percent of the participants, demonstrating the need for regular ophthalmologic examinations in cataract-operated patients.

SOURCE: Baranano AE, Wu J, Mazhar K, et al. (Los Angeles Latino Eye Study Group). Visual acuity outcomes after cataract extraction in adult Latinos: The Los Angeles Latino Eye Study. Ophthalmol 2007; Sep 7 [Epub ahead of print].

Epidemiological and Genetic Study of X-Linked Retinitis Pigmentosa

Researchers at the Technical University of Munich, the GSF-National Research Center for Environment and Health, Munich/Neuherberg, and the National Eye Clinic for the Visually Impaired in Denmark performed a national study of the prevalence and mutation spectrum in X-linked retinitis pigmentosa (XLRP), with genotype-phenotype comparisons.

The study comprised 96 affected males and 149 female carriers from 42 families representing all identified XLRP individuals in the Danish population (5.4 million inhabitants). RPGR and RP2 were screened for mutations in 34 families, the medical files of the patients were scrutinized and phenotype data were extracted.

The prevalence of affected males was estimated at 1:26,200 and 1:18,000 of female carriers. A rough estimate, however, indicated that the real prevalence of affected males was approximately 1:15,000. The cumulated life risk of development of XLRP in carriers was strongly age-dependent and included one-third of the carriers older than 60 years. Molecular analysis of RP2 and RPGR uncovered 28 different mutations in 33 of 34 index cases analyzed. Twelve patients carried a mutation in RP2, 12 in exons 1 to 14 and 9 in open reading frame (ORF) 15 of RPGR. Males with RP2 mutations tended to have higher degrees of myopia, lower visual acuities and more preserved visual fields than did males with RPGR mutations at the same age. No significant differences in phenotype were evident in age of onset and type of mutation in either RP2 or RPGR.

A very high mutation detection rate in familial cases makes genetic testing a valuable clinical tool for genetic counseling and prenatal testing. The proportion of RP2-mediated XLRP in the Danish population is higher and the proportion of RPGR-ORF15 is lower than reported in other studies. The authors believe, therefore, that strategies for diagnostic procedures should take into account the population-specific mutation spectrum.

SOURCE: Prokisch H, Hartig M, Hellinger R, et al. A population-based epidemiological and genetic study of x-linked retinitis pigmentosa. Invest Ophthalmol Vis Sci 2007;48(9):4012-8.

BRIEFLY

RESEARCH HIGHLIGHTS POTENTIAL BENEFITS OF TELEMEDICINE IN TREATING EYE DISEASE. Two studies presented at the American Academy of Ophthalmology's 2007 Annual Meeting suggest that telemedicine may have a significant role in diagnosing eye diseases, increasing patient compliance and providing patient access to quality care. In the first study, researchers examined the impact that telemedicine had on patients with diabetes being treated in multi-physician primary care practice. The study reviewed the number of patients with diabetes over the course of a year who had the recommended retinal examination before the installation of a telemedicine remote imaging system in the practice vs. the number of patients with diabetes who had a retinal examination in the two years following installation of the device. In the first year, only 15 percent of 1,257 diabetic patients in the study had a retinal examination. Two years after implementation of the telemedicine system, 71 percent of the 1,395 diabetic patients in the practice had a retinal exam. Significantly, of the observed increase, 66 percent was the result of an eye examination by a local ophthalmologist; only 33 percent was the result of remote evaluation. In a second study presented at the annual meeting, researchers concluded that there was a high level of agreement between diagnoses of retinopathy of prematurity (ROP) made in low birth-weight babies using ophthalmoscopy and image-based telemedicine examinations. Doctors at Columbia University gathered data on 206 eyes from 67 prematurely born infants, performing up to two sets of examinations on each child. In each instance, a pediatric ophthalmologist performed dilated indirect ophthalmoscopy on the infant to determine whether the he or she had ROP. Diagnoses were classified in four categories: no ROP, mild ROP, Type 2 prethreshold ROP and treatment-requiring ROP. Shortly after the physician's examination, a trained nurse captured retinal images of the same child using a wide-angle camera. After four to 12 months, the images were shown to the same doctor who performed ophthalmoscopy, to minimize any chance that the examiner could remember details. In 86 percent of the eyes, there was complete agreement between the diagnoses made by ophthalmoscopy and telemedicine. Among eyes where there was disagreement between the examination modalities, 12 cases involved clinically significant discrepancies regarding presence of Zone I disease or plus disease. Michael Chiang, MD, assistant professor of ophthalmology and biomedical informatics at the Columbia University College of Physicians and Surgeons and presenting author of the paper, suggests that telemedicine diagnosis may be more accurate in these cases, because images can be compared directly with standard photographic definitions of Zone I or plus disease.

IMPROVED CORNEAL SURGERY TECHNIQUE MAY PROVIDE ENHANCED TRANSPLANT SUCCESS. Dr. Massimo Busin, department head and professor of ophthalmology at the Villa Serena Hospital, Forli, Italy, described at the 2007 Annual Meeting of the American Academy of Ophthalmology in New Orleans a technique that significantly improved results in patients treated for endothelial disease of the cornea. While the standard approach has been penetrating keratoplasty, Descemet-stripping automated endothelial keratoplasy (DSAEK)--in which only endothelial tissue attached to a thin layer of deep stroma is transplanted and the normal structure of the recipient cornea is not disrupted--is increasingly preferred by corneal surgeons. Most patients undergoing DSAEK recover good vision within weeks and the risk of complications during and after surgery is minimized. A significant drawback of DSAEK, though, has been the limited survival of the transplanted endothelium, with a reduction of up to 50 percent of preoperative density as early as six months after DSAEK. Dr. Busin described a modified DSAEK technique developed by his group that resulted in rates of donor endothelial cell survival equivalent to that of PK. Their "pull-through" technique, said Dr. Busin, reduced the rate of endothelial cell loss in the transplanted tissue to an average of 23 percent at one year post-surgery, similar to values recorded after PK. The technique simplifies the DSAEK procedure and resolves the main obstacle that has delayed corneal surgeons' transition to DSAEK, Dr. Busin maintains.

NEOVISTA PRESENTS NEW DATA ON NOVEL WET AMD THERAPY. NeoVista, Inc., a privately held development-stage medical device company, released new data from an ongoing, nonrandomized, multi-center one-year feasibility study of the company's novel beta radiation epiretinal therapy for the wet form of age-related macular degeneration (AMD) at the 2007 annual AAO meeting. The company initiated the study to test the efficacy and safety of their novel therapy when used in combination with Avastin. In the study, 34 subjects with predominantly classic, minimally classic or occult (with no classic) choroidal neovascularization (CNV) received a single 24 Gy treatment of the epiretinal therapy in combination with two injections of Avastin: one dose at the time of radiation delivery and another one month later. After 12 months follow-up, subjects experienced a mean improvement of visual acuity of 13.1 letters using the Early Treatment Diabetic Retinopathy Study (ETDRS) test. A total of 96 percent of patients lost less than 15 letters of visual acuity; 15 percent required additional injections of Avastin throughout the year and 12 percent experienced adverse events related to the procedure (retinal tear, retinal detachment, subretinal hemorrhage and vitreous hemorrhage). Unlike previous forms of radiation therapy for wet AMD, NeoVista's technique delivers the peak dose of radiation directly to the lesion without damaging the underlying choroidal vasculature. Utilizing strontium-90, the focused radiation is delivered to a target area 3 mm deep and up to 5.4 mm in diameter. Importantly for patients, the systemic exposure to radiation is minimal because the effective dose to the entire body from NeoVista's epiretinal device is comparable to 15 minutes of exposure to the sun. For more information, go to www.neovistainc.com.


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