Review of Ophthalmology Online

Volume 5, Number 15

Monday, April 18, 2005

In this issue: (click heading to view article)

		Dry Eye in Diabetic Patients

		Estrogen Replacement Therapy and Retinal Vascular Caliber

		Oxidative DNA Damage in Pterygium

		Predicting Cataract Surgery Results Using a Macular Function Test

		Long Eyelashes in Children with Vernal Keratoconjunctivitis

		Briefly

Dry Eye in Diabetic Patients

Keratoconjunctivitis sicca (KCS) is significantly more common among diabetic patients than among members of the general population, and poor glycemic control correlates with increased artificial tear use in diabetic patients, according to a large prospective observational cohort study by Israel’s Hadassah University Hospital.

Researchers followed the electronic medical records of all patients in a district of Israel’s largest health maintenance organization who were older than 50 years (159,634 patients) between January 1 and December 31, 2003. Of those, 22,382 (14.0 percent) had diabetes. The proportion of ocular lubrication consumers was compared among diabetic and nondiabetic patients. All HbA1c laboratory tests performed by the diabetic patients were documented (41,910 tests), and glycemic control was correlated with the consumption of ocular lubrication.

After age and gender adjustment, results showed that a significantly higher percentage of diabetic patients (20.6 percent) received ocular lubrication, compared with nondiabetic patients (13.8 percent). The difference was significant for all age groups and for both sexes. A similar significant difference was prominent between diabetic and nondiabetic patients aged 60 to 89 years who were frequent users of ocular lubrication. Ocular lubrication consumption increased with poorer glycemic control (mean annual HbA1c levels). Multivariate analysis revealed that this effect was independent of age, sex, place of birth or place of residence.

SOURCE: Kaiserman I, Kaiserman N, Nakar S, Vinker S. Dry eye in diabetic patients. Am J Ophthalmol 2005;139(3):498-503.

Estrogen Replacement Therapy and Retinal Vascular Caliber

Estrogen replacement therapy (ERT) is associated with narrower retinal vessel diameters, independent of blood pressure (BP) and other vascular factors, according to a population-based cross-sectional study by the Centre for Eye Research Australia, University of Melbourne.

It is unclear whether ERT has an effect on the retinal circulation. Investigators in this study examined the association of ERT, female reproductive factors and retinal vascular caliber in women aged 43 to 84 years living in Beaver Dam, WI. They took retinal photographs of participants at the baseline examination and digitized them, and they measured the diameters of arterioles and venules. ERT and female reproductive factors were ascertained by interview.

Of the 2,469 women participants with data for analysis, 10.5 percent were current users of ERT and 7.4 percent were past users. After adjusting for age, BP, body mass index, smoking and other factors, women who were current users of ERT had narrower retinal arteriolar and venular diameters than those who were past users or who never used ERT, with mean arteriolar diameters of 167.6 µm for current users, 170.8 µm for past users, and 170.9 µm for those who never used ERT, and mean venular diameters of 239.9 µm for current users, 244.0 µm for past users, and 243.9 µm for those who never used ERT. A significant trend of increasing narrowing was evident for both arterioles and venules with increasing duration of ERT. Associations were somewhat stronger in younger women and women without a history of hypertension and cigarette smoking. Female reproductive factors (e.g., age of menarche and pregnancy) were not associated with retinal vessel diameters.

SOURCE: Wong TY, Knudtson MD, Klein BE, et al. Estrogen replacement therapy and retinal vascular caliber. Ophthalmol 2005;112(4):553-8.

Oxidative DNA Damage in Pterygium

Epidemiological evidence suggests that UV irradiation plays an important role in pterygial formation. The effects of UV irradiation are either direct, via UV phototoxic effect, or indirect, via formation of radical oxygen species (ROS). ROS injure cellular DNA, proteins and lipids. Among numerous types of oxidative DNA damage, the formation of 8-hydroxydeoxyguanosine (8-OHdG) presents only a minor fraction of UV-induced DNA damage, but it is a ubiquitous marker of oxidative stress.

To provide the molecular evidence of UV radiation, researchers at China’s Medical University Hospital and Taiwain’s National Cheng Kung University Hospital detected 8-OHdG in pterygium and discovered that human 8-oxoguanine glycosylase (hOGG1) is the key component responsible for the removal of 8-OHdG. To determine whether hOGG1 was expressed in pterygium, they also evaluated the enzyme.

Immunohistochemical staining using a monoclonal antibody to 8-OHdG and hOGG1 were performed on 52 pterygial specimens and six normal conjunctiva. Twelve pterygial specimens (23.1 percent) were positive for 8-OHdG staining, limited to the nuclei of the epithelial layer. No substantial staining was visible in the subepithelial fibrovascular layers. In pterygium with 8-OHdG staining, four of 11 specimens (36.4 percent) had hOGG1 expression. However, in pterygium without 8-OHdG staining, only three of 41 specimens (7.3 percent) had hOGG1 expression. The expression of hOGG1 was significantly associated with 8-OHdG positive staining. All normal controls were negative for 8-OHdG and hOGG1 staining.

The authors of the study believe that the results demonstrate for the first time that 8-OHdG exists in pterygium and represents oxidative stress in pterygium. The increased level of 8-OHdG in pterygium was not the result of decreased expression of hOGG1, while increased levels of 8-OHdG induced the expression of hOGG1.

SOURCE: Tsai Y-Y, Cheng Y-W, Lee H, et al. Oxidative DNA damage in pterygium. Mol Vis 2005;11(1):71-5.

Predicting Cataract Surgery Results Using a Macular Function Test

Belgian researchers recently conducted a prospective study to assess the predictive value of a macular function test in the preoperative evaluation of cataract patients.

The study comprised 396 uneventful consecutive cataract procedures performed by one surgeon from September 2000 to February 2001. Investigators recorded best corrected visual acuity (BCVA) and density and location of the lens opacities preoperatively, and they assessed macular function preoperatively using a Parinaud test at 12 cm with a hyperaddition of +8.0 diopters and extra illumination. They then compared postoperative BCVA with the results of the macular function test.

Of the 359 eyes (90.7 percent) that could read the Parinaud 1 line on the preoperative hyperaddition test, 338 (94.2 percent) attained a final BCVA of 20/25 or better and 356 (99.2 percent) attained a final BCVA of 20/30 or better. Twenty-five eyes that could not read Parinaud 1 and presented with a dense nuclear or posterior subcapsular cataract also achieved a BCVA of 20/25 or better. Three eyes could read Parinaud 1 preoperatively but did not attain a BCVA of 20/30 or better postoperatively; two of the eyes had macular edema and one had an opaque posterior capsule. The results suggest that this simple macular function test may be useful in predicting visual outcome after cataract surgery.

SOURCE: Vryghem JC, Van Cleynenbreugel H, Van Calster J, Leroux K. Predicting cataract surgery results using a macular function test. J Cataract Refract Surg 2004;30(11):2349-53.

Long Eyelashes in Children with Vernal Keratoconjunctivitis

Vernal keratoconjunctivitis (VKC) affects children mainly in temperate areas, with exacerbations in spring and summer. Eyelashes provide natural protection for the eyes from sunshine, wind, and foreign bodies. These factors induce a worsening of signs and symptoms in VKC, whereas mechanical protection of the eyes produces relief. The aim of this study by Anna Meyer Children's Hospital at the University of Florence, Italy, was to evaluate eyelash length in a large series of VKC patients and in age- and gender-matched healthy subjects.

Researchers measured upper eyelash length in 93 VKC patients (mean age, 8.7 years; range, 4 to 18 years) with a digital caliper. They evaluated history, clinical form, type of presentation, degree of severity and drug therapy, and determined skin tests and serum-specific immunoglobulin E for common allergens, serum-total immunoglobulin E, peripheral blood eosinophil counts and serum eosinophil cationic protein. Two age- and gender-matched control subjects for each VKC patient underwent the same eyelash measurement.

The upper eyelashes were significantly longer in VKC patients than in control subjects (mean +/- SD: 8.9 +/- 1.17 mm vs. 7.9 +/- 1.07 mm). In healthy subjects, a negative correlation occurred between eyelash length and age. With multivariate analysis, unlike control subjects, the eyelash length in VKC patients did not correlate with age, was positively correlated with the degree of severity of VKC, and was negatively correlated with the use of topical cyclosporine. Investigators believe that the ocular inflammation, by unknown chemical mediators, was likely responsible for the excessive eyelash growth. They suggest that their finding may represent a defensive mechanism against physical agents that might have a crucial role in the etiopathogenesis of VKC.

SOURCE: Pucci N, Novembre E, Lombardi E, et al. Long eyelashes in a case series of 93 children with vernal keratoconjunctivitis. Pediatrics 2005;115(1):e86-91.

BRIEFLY

FDA APPROVES BAUSCH & LOMB’S RETISERT ORPHAN DRUG. The FDA has approved Bausch & Lomb’s single-indication orphan drug Retisert (fluocinolone acetonide intravitreal implant, 0.59 mg), for the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye. Retisert is the first intravitreal drug implant developed to treat chronic non-infectious uveitis; it received FDA Fast Track status and Orphan Drug designation for this indication. The drug-delivery microtechnology of Retisert consists of a tiny drug reservoir designed to deliver sustained levels of fluocinolone acetonide, a corticosteroid, directly to the back of the eye for approximately 2.5 years (30 months). FDA approval was based on 34-week results from two three-year randomized, double-masked, multicenter clinical studies. The company plans to launch the product in mid-2005.

FCI EARNS MARKETING APPROVAL FOR SELF-RETAINING BICANALICULAR STENT. FCI Ophthalmics has received FDA approval to market its Self-Retaining Bicanaliculus Intubation Set (SRS) in the United States. The SRS allows physicians to intubate the canaliculi in the office while the patient is in the chair, using only topical anesthetic drops. It is made of medical grade silicone and is available in three lengths: 25mm, 30mm and 35mm. At each end of the stent is an anchor-shaped head that provides fixation; each head consists of two flexible winglets that fold inward during insertion through the punctum and spread out after passage through the junction of the common canaliculus and lacrimal sac, thus keeping the stent in place. A central marking on the tube acts as a reference point and allows verification of proper stent positioning following insertion. The winglets fold backward for easy removal of the stent from the ducts. For more information, go to www.fci-ophthalmics.com.

VIAGRA MAY CAUSE NONARTERITIC ISCHEMIC OPTIC NEUROPATHY. A study published in the Journal of Neuro-Ophthalmology describes seven patients aged 50 to 69 years who developed features of nonarteritic ischemic optic neuropathy (NAION) within 36 hours after taking Viagra (sildenafil citrate) for erectile dysfunction. Six of the patients had vision loss within 24 hours after use, and final visual acuity in the affected eye ranged from 20/20 to light perception; in one patient, both eyes were affected. All of the affected patients had pre-existing hypertension, diabetes, elevated cholesterol or hyperlipidemia. Seven similar cases were previously reported. Howard D. Pomeranz, the lead investigator in the study, believes that the association with NAION appears to involve all drugs of this type: reports have also surfaced implicating Cialis (tadalafil), another erectile dysfunction medication. He believes that the risk of NAION with erectile dysfunction drugs is still extremely small, but suggests that physicians prescribing these treatments be aware of their association with NAION and consider conducting examinations for patients with several heart disease risk factors.
SOURCE: Pomeranz, HD, Bhavsar AR. Nonarteritic ischemic optic neuropathy developing soon after use of sildenafil (Viagra): a report of seven new cases. J Neuro-Ophthalmol 2005;25(1):9-13.

OPHTHALMOLOGISTS AND PHYSICISTS DESIGN "BIONIC EYE" PROTOTYPE. Physicists and eye doctors at Stanford University’s Hansen Experimental Physics Laboratory, Department of Ophthalmology and Department of Neurobiology have designed an optoelectronic retinal prosthesis system capable of stimulating the retina with resolution corresponding to visual acuity of 20/80. At present, the system is being tested in laboratory rats only; the project is partly funded by the U.S. Air Force and VISX Corp., which licensed the technology through Stanford's Office of Technology Licensing. The researchers fashioned the device in an effort to bring artificial vision to those affected by retinal degeneration. The system aims to bypass the photoreceptors that die in degenerative retinal diseases and directly stimulate the inner retina with visual signals, using a small video camera mounted on transparent goggles, a small computer processor, a solar-powered battery implanted in the iris and a light-sensing 3-mm subretinal chip. The chip allows users to perceive 10 degrees of visual field at a time. Image amplification and other processing occur in the hardware outside the eye.


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