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May 2006

Journal Highlights

New Findings from Ophthalmology, AJO and Archives
June's Ophthalmology:
• Severe Ocular Injury Caused by Exploding Packets of Chuna
• Features That Predict Growth in Small Choroidal Melanocytic Lesions
• Two Hours of Daily Patching Shows Improvement in Amblyopia
• Fluocinolone Acetonide Implant Effective in Noninfectious Posterior Uveitis

May’s American Journal of Ophthalmology:
• The Accommodative Element in Accommodative Esotropia
• Transcaruncular Orbital Decompression for Optic Neuropathy in Graves’ Disease
• Corneal Keratocyte Deficits After PRK and LASIK

 Archives of Ophthalmology:
• Neurotransmitter Receptors and Neuromediators in Vernal Keratoconjunctivitis
• Cognitive Impairment in the Age-Related Eye Disease Study
• The Pediatric Vision Screener III: Detection of Strabismus in Children
• In Vitro Fluoroquinolone Resistance in Staphylococcal Endophthalmitis Isolates

Roundup of Other Journals:
• 60 Million People Will Have Glaucoma by 2010, and 79.6 Million by 2020
• Central Corneal Thickness Decreases With Age and Is Not Associated With Glaucoma Progression
• Poor Success Rates With Deep Sclerectomy, Mitomycin C in West Africa
• Phase 1 Trial of Encapsulated Cell Intraocular Implants in Retinitis Pigmentosa


Severe Ocular Injury Caused by Exploding Packets of Chuna
June’s issue

Agarwal et al. report severe ocular injuries resulting from exploding packets of chuna, a calcium hydroxide paste used in India as an additive to chewing tobacco. Chuna packets are made of thin plastic, and children often squeeze them like toys. When the packet bursts, chuna can spray out, coating the cornea and conjunctiva. It can also become lodged in the conjunctival fornices.

In this retrospective case series, the investigators studied 25 eyes of 21 patients, mostly children, with an average age of 8.4 years. Median visual acuity at presentation was light perception with projection. Patients were treated medically or with one or more surgeries including symblepharon release, amniotic membrane grafting, and allograft or autograft stem cell transplantation. Results indicated a poor prognosis, with median visual acuity 1/60 after a mean follow-up of 637 days.

The researchers urge manufacturers to print explicit warnings on the packets and recommend that doctors examine fornices of these patients and meticulously remove any residual particles.

Features That Predict Growth in Small Choroidal Melanocytic Lesions
June’s issue

A retrospective case study by Singh et al. has identified risk factors that predict growth of small choroidal melanocytic lesions. Researchers looked at size, location, diagnostic features and growth of small choroidal melanocytic lesions in 240 patients.

Within the follow-up period of 50 months, 11 patients (4.6 percent) demonstrated growth. These patients had lesions that were thicker (> 2 millimeters) and closer to the foveola (< 3 mm) than did the other patients. The researchers also noted significant correlations in growth related to sex (male), presence of symptoms and orange pigment. The investigators pointed out that previously published studies report an extreme variability of growth rates, ranging from 0 to 41 percent, which may be due to differences in inclusion criteria; this study included lesions of at least 1 mm.

While their data agree with previous reports, the authors call for a large, prospective study with broader inclusion criteria to provide improved stratification of risk estimates in patients with small melanocytic lesions.

Two Hours of Daily Patching Shows Improvement in Amblyopia
June’s issue

Findings by the Pediatric Eye Disease Investigator Group looking at treatment of moderate to severe amblyopia in children 3 to 7 years old demonstrate that occlusion of the sound eye improves amblyopia from strabismus, anisometropia, or both.

The study involved 180 patients with best-corrected amblyopic eye visual acuity of 20/40 to 20/400 who had worn spectacles for at least 16 weeks without improvement. These children were randomized to two hours of daily patching with one hour of near visual activities or to spectacles alone. After five weeks, the patching group had improved by an average of 0.6 lines more than the control group. At the end of the study (when visual acuity stopped improving), the patching group had improved by an average of 0.9 lines more than the control group. In a secondary cohort of patients with mild residual amblyopia following spectacle correction, a substantial proportion improved further with patching.

The authors conclude that many children with mild residual amblyopia after improvement with spectacles can benefit from occlusion therapy.

Fluocinolone Acetonide Implant Effective in Noninfectious Posterior Uveitis
June’s issue

Jaffe et al. evaluated an investigational intravitreal fluocinolone acetonide (FA) implant in patients with noninfectious posterior uveitis. In this prospective, multicenter study, 278 patients received either a 0.59-milligram or 2.1- mg implant; those with bilateral disease received the implant in the more severely affected eye.

Researchers showed that the device significantly reduced the uveitis recurrence rate and decreased the need for adjunctive therapy. In addition, visual acuity stabilized or improved, generally due to reductions in cystoid macular edema, when compared with nonimplanted fellow eyes. The efficacy of the 0.59-mg implant did not differ from the 2.1-mg implant. The most common side effects included increased intraocular pressure and cataract progression.

The authors conclude that the dramatic reduction in inflammation recurrences, and the stabilization, improvement in visual acuity and reduced need for adjunctive anti-inflammatory therapy all indicate a pronounced anti-inflammatory effect from the FA implant. Patients are currently being followed for an additional 2½ years to provide a more complete risk-to-benefit profile.


The Accommodative Element in Accommodative Esotropia
American Journal of Ophthalmology
May’s issue

The amount and effect of refractive correction in accommodative esotropia is still debated. Somer et al. evaluated the effect of reducing the hyperopic correction on the state of binocular accommodative response in fully accommodative esotropia and determined the “comfortable” amount of reduction in hyperopic correction.

The hyperopic corrections of children with a baseline refractive error of +1.5 to +5 D were gradually reduced in 0.5-D increments in this cohort study. Binocular accommodative ability was assessed by dynamic retinoscopy (monocular estimate method). Similar binocular accommodative responses were ascertained among patients with a baseline correction of ≤ 3 D of hyperopia and > 3 D of hyperopia, and patients were divided into two groups, group one (13 patients) and group two (18 patients), accordingly.

After a reduction of 2 D in group one and 1 D in group two, there was a decrease in accommodative response initially in the nondominant eye, while the dominant eye experienced a further reduction of 0.5 D. To overcome the accommodative lag, a reinstatement of a 0.5-D stronger hyperopic correction was required. Patients in group one tolerated a mean undercorrection of 2.37 D, and 77 percent were weaned off their spectacles. All of the children in group two were dependent upon spectacles at the completion of the study period. The final spectacle worn was a median of –1.67 D less than their full cycloplegic refraction.

A complete binocular accommodative ability seems to be a prerequisite for the establishment of “comfortable” hyperopic undercorrections. It does not seem to be a reasonable approach to consider further reductions in hyperopic correction in the presence of a bilateral decreased accommodative performance.

Transcaruncular Orbital Decompression for Optic Neuropathy in Graves’ Disease
American Journal of Ophthalmology
May’s issue

There are several alternate therapies for Graves’ ophthalmopathy with optic neuropathy. Liao et al. evaluated the efficacy of transcaruncular orbital apex decompression for Graves’ ophthalmopathy with compressive optic neuropathy nonresponsive to pulse corticosteroids.

Over the four-year period of this retrospective, interventional case series, transcaruncular orbital decompression was performed in 22 consecutive Graves’ ophthalmopathy patients (38 orbits) with compressive optic neuropathy refractory to pulse corticosteroids. The average period of corticosteroid treatment was 16.1 days. Main outcome measures were preoperative and postoperative best-corrected vision, Hertel exophthalmometry, 100-hue color sensation test, visual evoked potential, visual field and new-onset diplopia.

Visual acuity improved significantly from 1.08 logMAR preoperatively to 0.29 logMAR postoperatively (P < 0.0001). Average improvement in retinal sensitivity was 9.4 decibels, in P100 value of visual evoked potential was 27.5, and in “total errors” of the 100-hue test was 309.9 after surgery. Average retroplacement effect was 3.7 millimeters. Statistical analysis showed significant differences between preoperative and postoperative measurements for all of the above parameters (P < 0.0001). New-onset diplopia occurred in 38 percent of patients. There were no complications specifically attributable to the transcaruncular technique.

Advantages of the transcaruncular approach over other approaches in this specific situation included no external scar, less damage to adjacent tissue and wide exposure to the entire medial wall.

Corneal Keratocyte Deficits After PRK and LASIK
American Journal of Ophthalmology
May’s issue

The long-term effects of refractive surgical procedures on the cornea remain to be elucidated. Erie et al. from the Mayo Clinic measured changes in keratocyte density up to five years after photorefractive keratectomy and LASIK in a prospective, nonrandomized clinical trial.

Eighteen eyes of 12 patients received PRK to correct a mean refractive error of –3.73 D, and 17 eyes of 11 patients received LASIK to correct a mean refractive error of –6.56 D. Corneas were examined by using confocal microscopy before and six months, one year and two, three and five years after the procedures. Keratocyte densities were determined in five stromal layers in PRK patients and in six stromal layers in LASIK patients. Differences between preoperative and postoperative cell densities were compared by using paired t tests with Bonferroni correction for five comparisons.

After PRK, keratocyte density in the anterior stroma decreased by 40 percent, 42 percent, 45 percent and 47 percent at six months, two, three and five years, respectively (P < 0.001). At five years, keratocyte density decreased by 20 percent to 24 percent in the posterior stroma (P < 0.05).

After LASIK, keratocyte density in the stromal flap decreased by 22 percent at six months (P < 0.02) and 37 percent at five years (P < 0.001). Keratocyte density in the anterior retroablation zone decreased by 18 percent (P < 0.001) at one year and 42 percent (P < 0.001) at five years. And in the posterior stroma, keratocyte density decreased by 19 percent to 22 percent (P < 0.05) at five years.

Keratocyte density decreases for at least five years in the anterior stroma after PRK and in the stromal flap and the retroablation zone after LASIK. An accompanying editorial discusses further the significance of the findings.

Neurotransmitter Receptors and Neuromediators in Vernal Keratoconjunctivitis
Archives of Ophthalmology
April’s issue

Motterle et al. examined the expression of neurotransmitters and neurotransmitter receptors in vernal keratoconjunctivitis (VKC) tissues to evaluate whether neurogenic inflammation plays a role in this ocular atopic-related disorder.

Conjunctival biopsies were obtained from eight VKC patients with active inflammation and from four healthy subjects and processed for immunohistochemistry using anti-M1-, M2- and M3- muscarinic receptors (M-R), and beta1-adrenergic receptor (beta1-AR), vasoactive intestinal peptide (VIP), nerve growth factor (NGF) and PGP 9.5, a marker of nerve fibers.

In the conjunctival epithelium of VKC patients, M1-R, NGF and PGP 9.5 expression were decreased, whereas M2-R, M3-R and beta1-AR were irregularly distributed compared with controls. Conversely, neurotransmitter receptors, neurotransmitters, VIP, NGF and PGP 9.5 expression were increased in the substantia propria–localized infiltrate of VKC compared with healthy tissue.

The authors conclude that the inflamed conjunctiva of VKC patients demonstrated an obvious alteration in muscarinic and beta1-adrenergic receptors, and VIP, PGP 9.5 and NGF expression. These results substantiate the involvement of an autonomic dysfunction in the pathogenesis of VKC, explaining the mucus hypersecretion, goblet cell hyperplasia and conjunctival hyperreactivity typical of this disease.

Cognitive Impairment in the Age-Related Eye Disease Study
Archives of Ophthalmology
April’s issue

The Age-Related Eye Disease Study (AREDS) research group examined potential associations between cognitive function/impairment and age-related macular degeneration and visual impairment.

AREDS is an 11-center natural history study of AMD and age-related cataract. The AREDS Cognitive Function Battery, which consists of six neuropsychological tests measuring performance in several cognitive domains, was administered to 2,946 participants. The macular status of participants at the time of cognitive function assessment ranged from essentially no macular abnormality in either eye to advanced AMD in at least one eye.

Mean cognitive function instrument scores significantly decreased with increased macular abnormality and with increased visual impairment. After covariate adjustment, increased macular abnormalities reduced mean cognitive function scores as measured by the Modified Mini Mental Status Examination, a global measure of cognitive function, and the Wechsler Logical Memory Scale (3MS), a measure of immediate and delayed recall. Reduced vision was found to be associated with reduced mean cognitive function scores as measured by the 3MS and letter and verbal fluency.

The results suggest a possible association of advanced AMD and visual acuity with cognitive impairment in older persons.

The Pediatric Vision Screener III: Detection of Strabismus in Children
Archives of Ophthalmology
April’s issue

Amblyopia often eludes detection by primary care providers, resulting in preventable vision loss in hundreds of thousands of children. At present no automated approach to screening shows satisfactory levels of sensitivity and specificity to identify children at risk for developing amblyopia. Nassif et al. tested a Pediatric Vision Screener (PVS) prototype that measures binocular alignment by detecting foveal fixation in both eyes simultaneously using binocular retinal birefringence scanning.

Gold-standard orthoptic evaluations were performed on 77 children aged 2 to 18 to identify those at risk for amblyopia. Based on the examination, 40 children were classified as controls (no strabismus or anisometropia) and 37 were classified as patients. Patients and controls were then scanned with the PVS, which obtained five alignment measurements over 2.5 seconds to generate a “binocularity” score. Binocularity as determined by the PVS was > 65 percent for all controls and < 52 percent for all patients.

The authors conclude that binocular retinal birefringence scanning shows potential for automated identification of children at risk for amblyopia in the primary care setting. More study will be required to determine whether this approach will be effective outside the laboratory environment, and whether anisometropic amblyopia can be detected consistently using this approach.

In Vitro Fluoroquinolone Resistance in Staphylococcal Endophthalmitis Isolates
Archives of Ophthalmology
April’s issue

Miller et al. examined the emerging in vitro resistance to gatifloxacin and moxifloxacin among coagulase-negative staphylococci (CNS) recovered from patients with postoperative endophthalmitis.

In vitro susceptibility and cross resistance of 111 CNS recovered from vitreous during the 15-year period from 1990 to 2004 were determined for gatifloxacin, moxifloxacin, levofloxacin, ofloxacin and ciprofloxacin.

In vitro susceptibilities (percent sensitive) in descending order were: 74.5 percent (gatifloxacin), 72.1 percent (moxifloxacin), 69.3 percent (levofloxacin), 65.6 percent (ciprofloxacin) and 60.4 percent (ofloxacin). More than 65 percent of the CNS resistant to ciprofloxacin (n = 38) demonstrated in vitro cross resistance to gatifloxacin (66 percent, 25/38) and moxifloxacin (71 percent, 27/38). During the initial five years (1990–1994), 97 percent of the CNS isolates were sensitive to both gatifloxacin and moxifloxacin. MIC90s were 0.19 micrograms/milliliter and 0.12 µg/ ml, respectively. During the last five-year period (2000–2004), the percentage of sensitive CNS isolates declined to 65.4 percent for both gatifloxacin and moxifloxacin (P = 0.016, 95 CI). MIC90s were > 32 µg/ml for both drugs.

The authors conclude that gatifloxacin and moxifloxacin demonstrated an overall in vitro efficacy of less than 80 percent for CNS isolates recovered from vitreous samples in this study. Resistance increased significantly during the last five years. Declining in vitro susceptibility to gatifloxacin and moxifloxacin may have important implications for the prevention and treatment of endophthalmitis.


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

60 Million People Will Have Glaucoma by 2010, and 79.6 Million by 2020
British Journal of Ophthalmology

While Quigley and Broman may not possess a crystal ball, they do have access to data from population-based studies. Reviewing these data using prevalence models, the authors estimated the number of people who will have open-angle glaucoma (OAG) and angle-closure glaucoma (ACG) in 2010 and 2020.

They projected that by 2010, 60 million people will have either OAG or ACG, and that glaucoma will be the second leading cause of world blindness. (Their model also predicted that 2.79 million people will have OAG in the United States in 2010.) This figure will increase to 79.6 million by 2020, and of these, 74 percent will have OAG. Women will comprise 55 percent of OAG cases, 70 percent of ACG cases and 59 percent of all glaucoma cases in 2010. Asians will constitute 47 percent of those with glaucoma and 87 percent of those with ACG. Finally in 2010, 4.5 million people with OAG will experience bilateral blindness, and 3.9 million people with ACG will have bilateral blindness. In 2020, these figures will increase to 5.9 million people and 5.3 million people, respectively.

Central Corneal Thickness Decreases With Age and Is Not Associated With Glaucoma Progression
British Journal of Ophthalmology
Published online Feb. 15, 2006

Recent research has shown that central corneal thickness (CCT) is a key risk factor for the development and severity of glaucoma, and that the clinical use of CCT measurements affects glaucoma management strategy in 15 percent of patients. Weizer et al. conducted a study to determine if CCT changes over time, and whether this change is associated with glaucoma progression.

In two visits 8.2 years apart, the authors extensively examined 39 patients (64 eyes) who had open-angle glaucoma, ocular hypertension, glaucoma suspect status or a normal eye exam. They measured CCT and looked at such factors as a history of glaucoma, presence of diabetes, vertical and horizontal cup-to-disc ratio and the number of glaucoma medications prescribed.

They found that CCT decreased over time, with a greater decrease in patients with primary open-angle glaucoma. However, the CCT decrease did not seem to be related to glaucoma progression. The authors call for further study to determine why mean CCT appears to change over time. They recommend ophthalmologists consider performing pachymetry more than once in a patient’s lifetime since a CCT change may influence that patient’s therapy.

Poor Success Rates With Deep Sclerectomy, Mitomycin C in West Africa
British Journal of Ophthalmology

In the first report on deep sclerectomy (DS) from West Africa, Mielke et al. have found that the success rate with this procedure is low. Additionally, the study did not achieve sufficient power to determine whether low dose mitomycin C (MMC) could increase the DS success rates.

The researchers conducted a prospective, randomized, controlled trial on 39 eyes of 39 Nigerian patients with medically uncontrolled primary open-angle glaucoma undergoing DS. The patients were randomized into receiving intraoperative MMC 0.25 milligrams/milliliter for two minutes at the end of the procedure (18 patients) or a control group that did not receive MMC (21 patients).

They found that while low dose MMC was safe, it did not appear to increase the success rate of DS in this population. They called the success rates of DS in both groups “disappointingly low,” with IOP control only achieved through medications or further procedures. They conclude that without facilities for Nd:YAG laser goniopuncture and regular follow-up, the DS procedure has poor success rates in this population.

Phase 1 Trial of Encapsulated Cell Intraocular Implants in Retinitis Pigmentosa
Proceedings of the National Academy of Sciences

A phase 1 trial by Sieving et al. utilizing encapsulated cells of human ciliary neurotrophic factor (CNTF) surgically implanted into the vitreous of the eye of patients with retinitis pigmentosa (RP) found that the approach was safe for the human retina, even with severely compromised photoreceptors.

The researchers utilized neurotrophic factors because of their ability to retard progression of neurodegenerative diseases; these factors have proven to be effective in slowing photoreceptor degeneration in animal models of RP.

In the study, 10 patients received CNTF implants in one eye. When surgeons removed the implants after six months, the implants contained viable cells with minimal cell loss and gave CNTF output at levels previously shown to be effective for retinal degeneration in dogs with rod-cone dysplasia type 1. Since this was a phase 1 trial, it was not designed to judge visual acuity. However, seven eyes did reach and maintain improved acuities of 10 to 15 letters in reading charts.


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

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