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April 2006

Journal Highlights

New Findings from Ophthalmology, AJO and Archives

May's Ophthalmology:
• Sodium Hyaluronate and Trabeculectomy
• Delayed Presbyopia and First- Generation PRK
• Repeated Intravitreal Triamcinolone Acetonide for Diabetic Macular Edema
• Early Orbital Decompression for Graves’ Orbitopathy
• Vitreous Hemorrhage in Children

April’s American Journal of Ophthalmology:
• Complications of Intravitreal Triamcinolone for Macular Edema
• Long-Term Follow-Up of Intermediate Uveitis in Children
• Lisinopril for Inflammatory Macular Edema Ineffective
• Conventional vs. Wavefront-Guided Myopic LASIK Re-treatment

 Archives of Ophthalmology:
• Azithromycin Better Than Tetracycline for Trichiasis
• The Macular Hole: Histopathologic Studies

Roundup of Other Journals:
• Artificial Tears and Visual Field Testing Reliability in Glaucoma Patients With Dry Eye
• Drusen Complement Components Promote Choroidal Neovascularization
• Antioxidants Reduce Risk of Age-Related Macular Degeneration
• Refractive Expectations of Cataract Surgery


Sodium Hyaluronate and Trabeculectomy
May’s issue

Lopes et al. have found that subconjunctival sodium hyaluronate 2.3 percent (Healon 5) does not increase the intermediate-term success rate of glaucoma filtering surgery. However, this approach is associated with the formation of more diffuse blebs.

In a prospective randomized trial, 55 patients underwent routine trabeculectomy, with 28 patients receiving Healon 5 injected between the scleral and conjunctival flap at the conclusion of surgery; and a 27-patient control group receiving a similar injection with balanced salt solution. Complete success rates (measured as IOP equal to or less than 21 mmHg without antiglaucoma medication) were 77.8 percent for the study group and 84 percent for the control group 12 months after surgery. Qualified success rates (IOP 21 mmHg or less with or without antiglaucoma medication) were 88.9 percent for the study group and 92 percent for the control group.

The study group had more diffuse blebs than the control group. The authors caution that the small sample size should be considered before making generalizations on these findings.

Delayed Presbyopia and First- Generation PRK
May’s issue

A study by Artola et al. evaluating the eyes of patients over 40 years old who underwent PRK with first-generation technology indicates delayed presbyopia symptoms and improved near acuity, but at the expense of reduced overall optical quality.

The authors conducted a retrospective study evaluating uncorrected near visual acuity, accommodation, corneal aberrations and optical quality of retinal image in presbyopic eyes in 10 post-PRK patients and 10 normal patients. They found the optical quality of the retinal image was reduced at low contrast with increased aberrations attributed to the corneal surface. However, both measured subjective accommodation and near acuity were greater than expected, prompting the authors to postulate that PRK causes a multifocal effect, which reduces the quality of the retinal image but enhances near acuity.

In light of these findings, the authors suggest it may be possible to enhance depth of field and delay presbyopia symptoms by purposefully introducing fixed levels of additional spherical aberration into the eye. Prospective validation is needed.

Repeated Intravitreal Triamcinolone Acetonide for Diabetic Macular Edema
May’s issue

Data from a pilot study by Jonas et al. suggest that repeated intravitreal injections of approximately 20 milligrams of triamcinolone acetonide to treat diffuse diabetic macular edema are associated with improvement in visual acuity in responders to previous intravitreal injection. This effect, and a rise in IOP as a side-effect, lasts six to eight months after each injection, without signs of marked tachyphylaxis.

The study group included 19 patients who had previously responded to an intravitreal injection of triamcinolone acetonide. All received a second injection and some received a third follow-up injection. The control group, which consisted of 31 patients with diffuse diabetic macular edema, did not receive treatment during the follow-up period.

After the second and third injections in the study group, visual acuity increased significantly. The authors conclude that eyes showing a functional improvement after an intravitreal triamcinolone acetonide injection may receive a reinjection if visual acuity deteriorates.

Early Orbital Decompression for Graves’ Orbitopathy
May’s issue

It has been hypothesized that early rehabilitative orbital decompression in Graves’ orbitopathy (GO) leads to a more effective postoperative outcome than the same intervention performed at a later stage. However, a study by Baldeschi et al. found no substance to this hypothesis and, in fact, determined early treatment was associated with a higher risk of postdecompression diplopia.

The authors reviewed 125 medical records of GO patients who had undergone a three-wall orbital decompression at one institution between 1990 and 2000. Patients were divided into group one, which had GO for less than four years, and group two, which had GO for more than four years.

They found no difference in surgical outcomes between the two groups, although postdecompression diplopia was significantly more frequent in group one. The authors cite several challenges to conducting a prospective clinical trial, but add it is necessary, given this current study may have been biased by systemic corticosteroid use and orbital radiotherapy.

Vitreous Hemorrhage in Children
May’s issue

Spirn et al. have shown that vitreous hemorrhage has multiple etiologies in the pediatric population. In fact, the authors were able to identify 26 different causes of vitreous hemorrhage not secondary to active retinopathy of prematurity (ROP) in 168 patients (186 eyes), less than 18 years of age, seen over eight consecutive years.

Penetrating and nonpenetrating trauma accounted for the majority of cases (54.3 percent). When combined with occult causes of trauma—specifically shaken baby syndrome and birth trauma—and postoperative patients, trauma accounted for approximately 75 percent of cases. Spontaneous causes constituted approximately 25 percent of cases, with regressed ROP the most frequent.

Visual outcomes were poorest with penetrating trauma and best with regressed ROP. The authors also found that outcomes in children with vitreous hemorrhage were generally poor and appear to be more dependent on etiology than age.


Complications of Intravitreal Triamcinolone for Macular Edema
American Journal of Ophthalmology
April’s issue

Intravitreal triamcinolone has been used in the treatment of many eye diseases but has been poorly described with long-term follow-up data. John Thompson evaluated complications and results of intravitreal triamcinolone acetonide for treatment of macular edema in an interventional, consecutive, retrospective case series.

Ninety-three eyes with macular edema arising from retinovascular etiologies were treated with 4 milligrams of intravitreal triamcinolone. Eyes were monitored after injection for visual acuity changes and complications, including cataract formation and increase in IOP. Cataract progression was analyzed by linear regression analysis of lens scores from lens opacity standards.

The mean visual acuity improved one to two months after injection (P < 0.001) and was 20/100 at the final examination (P = 0.006) at a mean of 1.2 years after injection. Complications included a severe, culture-negative inflammatory reaction in one eye (1.1 percent). IOP increased to 30 mmHg or more in nine eyes (9.7 percent) between one and 140 days after injection and was more frequent in eyes receiving one or more preinjection glaucoma drops. Nuclear sclerosis increased at a rate of 0.175 U per year, posterior subcapsular cataracts at 0.423 U per year and cortical cataracts at 0.045 U per year. Posterior subcapsular cataract increased by >1 U or required cataract surgery in 45.2 percent of eyes followed at least one year.

Intravitreal triamcinolone improves visual acuity in most eyes, but eyes must be monitored carefully for increase in IOP. Posterior subcapsular cataract formation becomes visually significant in almost half of eyes by one year after injection.

Long-Term Follow-Up of Intermediate Uveitis in Children
American Journal of Ophthalmology
April’s issue

Intermediate uveitis in children is an uncommon disease, and there are limited data on the long-term prognosis. De Boer et al. analyzed the clinical manifestations, remissions and visual prognosis of intermediate uveitis in children and identified the risk factors for poor visual outcome.

This was a retrospective cohort of 32 consecutive patients with intermediate uveitis with disease onset before age 16. Numerous variables were assessed, including age and gender distribution, laboratory data, the presence of systemic disease, onset and course of ocular inflammation, clinical features and complications, therapeutic strategies and outcomes, remission and final visual acuity, and characteristics associated with poor visual outcome.

Bilateral involvement was observed in 94 percent of the patients. Remission was observed in seven out of 15 patients (47 percent) with completed follow- up of five years. For all 32 subjects, the mean time to remission was 6.4 years. Visual outcome was favorable as only three patients developed unilateral acuity of less than 0.1 after five-year follow-up, and no additional blind eyes manifested.

No associated systemic diseases were established. Optic disc edema was the most frequent complication observed (71 percent). Cystoid macular edema was observed in 44 percent of the patients and was the most common cause of visual loss.

Intermediate uveitis of childhood might exhibit a self-limiting course of several years. Visual loss was not severe despite the high rate of serious complications.

Lisinopril for Inflammatory Macular Edema Ineffective
American Journal of Ophthalmology
April’s issue

Van Kooij et al. analyzed the effect of the ACE inhibitor lisinopril on inflammatory cystoid macular edema and visual acuity.

In a randomized, double-masked, placebo-controlled, cross-over trial, 40 patients with inflammatory cystoid macular edema were given either lisinopril, 10 milligrams, or placebo, daily, for three months.

After two months of a lisinopril/ placebo-free wash-out period, patients were transferred to the opposite study arm for three months.

Fluorescein angiography was performed to evaluate the retina. Cystoid macular edema, best-corrected visual acuity and contrast sensitivity were considered.

Lisinopril had no effect on cystoid macular edema, visual acuity, papillary leakage, retinal vasculitis or choroidal leakage. In a subgroup analysis, there was a decrease in blood pressure with lisinopril compared with placebo (P = 0.02) and a decrease in morning urinary albumin excretion with lisinopril compared to placebo (P = 0.003).

Although lisinopril appeared to have no effect on inflammatory cystoid macular edema and visual acuity, there seemed to be a positive effect on the vascular system.

Conventional vs. Wavefront-Guided Myopic LASIK Re-treatment
American Journal of Ophthalmology
April’s issue

The usefulness of wavefront-guided LASIK remains controversial. Jin and Merkley assessed the clinical outcomes of conventional and wavefront-guided myopic LASIK re-treatment.

This retrospective, nonrandomized case series involved a cohort of 97 eyes undergoing LASIK re-treatment for residual myopia following primary LASIK.

The eyes were divided into two groups: conventional re-treatment (CR) group (n = 74) and wavefront-guided re-treatment (WR) group (n = 23).The mean follow-up was 8.9 months after re-treatment.

The mean pre-retreatment spherical equivalent (SE) was –0.93 diopters in the CR group and –0.84 D in the WR group (P = 0.409). At the last visit, the mean SE was –0.19 D and +0.32 D, respectively (P = 0.000). An SE of ± 0.50 D was achieved in 92 percent (68 of 74) of CR eyes and 65 percent (15 of 23) of WR eyes. In the CR group, 85 percent of the eyes had an uncorrected visual acuity of 20/20, and 99 percent had a UCVA of 20/40 or better; in the WR group, the same UCVA scores were achieved by 35 percent and 100 percent of the patients, respectively. None of the CR eyes and 17 percent of WR eyes lost two lines of BCVA. Nine percent of CR eyes and 30 percent of WR eyes had optical symptoms before re-treatment; those numbers were subsequently reduced to 1 percent and 4 percent, respectively.

In the study period with the equipment used by the authors, the results showed that conventional LASIK re-treatment was superior to wavefront-guided LASIK re-treatment in both efficacy and safety.

Azithromycin Better Than Tetracycline for Trichiasis
Archives of Ophthalmology
March’s issue

West et al. conducted a randomized clinical trial in 1,452 Ethiopian patients presenting for trichiasis surgery to determine if postsurgical antibiotic treatment would reduce recurrence.

Moreover, the study evaluated any additional benefit of lower recurrence with treating the patient’s family as well, compared with treating just the patient alone.

About 484 patients were randomized to one of three arms: a single 1 gram dose of oral azithromycin per patient, a single 1 gram dose of azithromycin for the patient as well as all family members, or four to six weeks of topical tetracycline.

At all follow-up visits, the surgical eye was evaluated for recurrence of trichiasis. Ninety-eight percent of patients were followed to one year.

The cases had severe trichiasis at baseline, with more than half having five or more lashes touching the cornea. At one year, patients receiving azithromycin had significantly fewer recurrences compared with patients receiving topical tetracycline.

There was no significant benefit from extending treatment to family members, compared with treating patients alone.

The authors conclude that a single dose of azithromycin immediately after surgery offered significant reduction in recurrence of trichiasis out to one year and should be part of trachoma surgical programs.

The Macular Hole: Histopathologic Studies
Archives of Ophthalmology
March’s issue

W.R. Green studied 815 ocular fluid specimens obtained after vitreous surgery for macular holes.

Cellular or fibrocellular fragments were observed in only 22.5 percent of cases. In 92 cases surgically isolated tissue was studied by transmission electron microscopy.

The organization of the tissues supports the role of the cortical vitreous in the pathogenesis of macular holes: a layer of cortical vitreous was present in 18; a cellular layer along one surface of the cortical vitreous layer in 18; a layer of cortical vitreous along the internal surface of the internal limiting lamina of the retina in 10; and a layer of cortical vitreous was interposed between the internal limiting lamina of the retina and a cellular layer on the internal surface of the internal limiting lamina of the retina in nine cases.

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

Artificial Tears and Visual Field Testing Reliability
in Glaucoma Patients With Dry Eye
Published online Jan. 27, 2006

In many instances, the value of a visual field test is only as good as the reliability of the patient’s response. Patients taking antiglaucoma drugs may experience inflammatory effects on the ocular surface, leading to variations of visual acuity. In addition, a precorneal tear film disturbance, which can be the result of dry eye, may cause a deterioration in visual quality.

Yenice et al. examined the effects of artificial tear administration on automated perimetry of primary open-angle glaucoma patients with dry eye. After a pretest visit that included an automated perimetry exam, the 40 study participants used artificial tears four times a day in both eyes for one week. Repeated visual field testing showed significant improvement in reliability parameters and visual field indices, while the number of depressed points at the probability levels at total deviation plot and in pattern deviation plot decreased significantly.

The investigators conclude that elderly patients with open-angle glaucoma and dry eye symptoms should use artificial tears prior to undergoing automated perimetry to increase the reliability of this visual field test.

Drusen Complement Components Promote Choroidal Neovascularization
Proceedings of the National Academy of Sciences

Nozaki et al. have demonstrated a mechanistic basis for the clinical observation that drusen predisposes patients to choroidal neovascularization in age-related macular degeneration. Previous research has shown that complement components C3 and C5 are constituents of drusen in patients with AMD, indicating that these inflammatory proteins may play a role in the development of AMD. The current study demonstrates that bioactive fragments of C3 and C5, namely C3a and C5a, are not only present in drusen of patients with AMD but actually induce vascular endothelial growth factor (VEGF) expression both in vitro and in vivo.

The authors also were able to show that C3a and C5a are generated early in the course of laser-induced CNV, which is an accelerated model of neovascular AMD caused by VEGF and recruitment of leukocytes into the choroid.

Finally, the authors demonstrated that genetic ablation of C3a or C5a receptors reduces VEGF expression, leukocyte recruitment and CNV formation after laser injury.

They conclude these findings show an immunological role in angiogenesis and may provide therapeutic targets for treating AMD.

Antioxidants Reduce Risk of Age-Related Macular Degeneration
The Journal of the American Medical Association

A study by van Leeuwen et al. has found that high dietary intake of vitamin E and zinc is associated with a substantially reduced risk of age-related macular degeneration in elderly individuals. In addition, an above-median intake of the combination of vitamins C and E, beta carotene and zinc was associated with a 35 percent lower risk of AMD.

The investigators assessed dietary intake at baseline in the Rotterdam Study (1990 to 1993) of persons 55 years or older in Rotterdam, the Netherlands. Of the 5,836 persons at risk for AMD at baseline, 4,765 had reliable dietary data and 4,170 participated in the mean follow-up period of eight years. Incident AMD occurred in 560 participants, with an inverse association of dietary intake of both vitamin E and zinc.

The authors note these nutrients are easily found in dietary sources: beta carotene in carrots, kale and spinach, zinc in fish, whole grains and dairy products, vitamin C in citrus fruit, peppers and broccoli, and vitamin E in whole grains, eggs and nuts.

Refractive Expectations of Cataract Surgery
Journal of Cataract and Refractive Surgery

A patient’s refractive state prior to undergoing cataract surgery greatly influences his or her expectations concerning refractive outcomes: if the patient wore glasses for distance, near vision or both prior to surgery, he or she will expect to continue needing spectacles after surgery, whereas those who do not wear spectacles prior to surgery do not expect to need them following the procedure.

Hawker et al. gathered these perceptions from a prospective questionnaire study of 189 patients with a mean age of 74 years (64 percent were women). The surgeons expressed surprise that most patients expected to wear glasses for distance and near correction following cataract surgery given advances in intraocular lens implantation and the fact that 62 percent of the patients had spoken to someone who had already undergone the procedure.

The authors conclude that patients not already wearing spectacles prior to surgery did not expect to need them and suggests that this group is at particular risk for refractive disappointment and complaint. They recommend that surgeons obtaining consent should know the patient’s preoperative refractive state and make it a point to discuss refractive planning and likely refractive outcome. This will help reduce disappointment.

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