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Journal Highlights

New Findings from Ophthalmology, AJO and Archives
 
 

June’s Ophthalmology:

Noncompliance Among Glaucoma Patients Is Common, Yet Clinical Implications Remain Unclear

Use of OCT Technology to Visualize Anterior Chamber Angle Dynamics

Does VEGF Have a Role in the Pathogenesis of Pterygia?

Posterior Subtenon’s Triamcinolone Injection Combined With Focal Laser for Diabetic Macular Edema

Postop Measured IOP Decreases Independently as a Result of the Lamellar Corneal Flap

May’s American Journal of Ophthalmology:

Reducing Corneal Astigmatism at the Time of Cataract Surgery

Asymptomatic Clinical Retinal Detachments Might Be Observed

Two Approaches to Treating Diabetic Macular Edema

Reduction of Foveal Thickness and Visual Acuity in DME Treated With Intravitreal Triamcinolone

April’s Archives of Ophthalmology:

Amblyopia Treatment in Children Aged 7 to 17 Years Old

Researchers Identify a TIMP-3 Mutation Associated With Sorsby Fundus Dystrophy

OCT Longitudinal Evaluation of Retinal Nerve Fiber Layer Thickness in Glaucoma

Roundup of Other Journals:

Noninvasive Identification of Early Coronary Artery Disease

Cocaine and Phenylephrine Eye Drops as a Possible Marker for Diagnosing Parkinson’s Disease

Measuring Ocular Rigidity in Living Human Eyes

Thick Acellular Human Dermis for Lower Eyelid Reconstruction

Previews

Noncompliance Among Glaucoma Patients Is Common, Yet Clinical Implications Remain Unclear
Ophthalmology
June’s issue

Is it worthwhile to improve hypotensive therapy compliance in patients with glaucoma?

Findings from a report by Olthoff et al. indicate that the jury still may be out. A literature search revealed noncompliance was common—with 5 percent to 80 percent of patients reporting they deviate from their prescribed medication regimen—yet it was not possible to determine the impact of this noncompliance on clinical outcome.

The authors questioned the value of assessing the clinical relevance of noncompliance by comparing patients’ dosing history to the prescribed number of doses because this approach did not take into account either the pharmacological properties of the drug or the pathophysiologic aspect of the disease.

The “gold standard” for obtaining an objective picture of a patient’s dosing history is a medication monitor, but this isn’t always practical.

The authors conclude that while there are no determinants sensitive enough to identify potential noncompliers, physicians who suspect noncompliance can incorporate patient education and a system to prevent forgetting doses to enhance compliance.

Use of OCT Technology to Visualize Anterior Chamber Angle Dynamics
Ophthalmology
June’s issue

While optical coherence tomography was originally designed to examine retinal nerve fiber layer and retinal thickness, Leung et al. have found another use for this technology—scanning in fine detail the anterior segment structures in order to assess glaucoma patients. 

Through use of OCT, they discovered that changes in anterior chamber angle configuration correlated to the underlying pathophysiology in different forms of angle-closure glaucoma.

The investigators assessed different patterns of angle configuration before and after laser peripheral iridotomy and argon laser peripheral iridoplasty in three glaucoma patients.

Visualization of the changes in the angle configurations demonstrated the importance of anatomic spatial relationships of the iridocorneoscleral junction in relationship to underlying pathophysiology in different forms of angle-closure glaucoma.

The authors conclude that OCT may prove valuable in this clinical setting because, unlike ultrasound biomicroscopy, which is a close-contact, immersion technique requiring supine positioning of patients, OCT is non-contact.  

Does VEGF Have a Role in the Pathogenesis of Pterygia?
Ophthalmology
June’s issue

Gebhardt et al. studied the distribution of vascular endothelial growth factor isoforms and receptors VEGFR-1 and VEGFR-2 in pterygia and compared it with the distribution in healthy conjunctiva.

They found that VEGF and VEGFR expression was similar between limbal and pterygial epithelial cells—implying that pterygia arise from limbal epithelial cells and that VEGF may play an active role in the physiology of conjunctival epithelial cells. 

In the tissue analysis, not only did limbal tissue contain amounts of VEGF comparable to pterygia, but the VEGF receptors VEGFR-1 and -2 also were expressed in about the same amounts in the corneal limbus and in pterygium; the expression of both receptors was lower in normal healthy conjunctiva.

The findings from this study suggest that the VEGF content of pterygia reflect the limbal origin of pterygia with higher levels than in normal healthy conjunctiva. The authors conclude that these findings call into question studies that use normal healthy conjunctivae as the reference control for any analysis of pterygia.

Posterior Subtenon’s Triamcinolone Injection Combined With Focal Laser for Diabetic Macular Edema
Ophthalmology
June’s issue

A prospective, randomized study by Tunc et al. found that posterior subtenon’s triamcinolone acetonide injection may improve early visual outcome in diffuse diabetic macular edema when combined with focal laser.

The investigators randomized 30 eyes to receive macular focal and grid laser photocoagulation (MP) and 30 eyes to receive focal laser photocoagulation combined with posterior subtenon’s triamcinolone injection (FL+PSTI).

The clinical evaluation was based on stereoscopic retinal examination, color fundus photographs and fluorescein angiography.

Results indicate that the early (18 weeks) clinical improvement rate and grade was higher in the combined FL+ PSTI group compared with the MP group. In addition, FL+PSTI provided significant improvement in visual acuity compared with the baseline Early Treatment Diabetic Retinopathy Study acuity scores at 18 weeks.

The investigators conclude that while the posterior subtenon’s injection technique is relatively safe and minimally invasive, long-term effects of combined FL+PSTI treatment remain unclear. They call for further studies in larger populations to verify the effectiveness of this treatment approach.

Postop Measured IOP Decreases Independently as a Result of the Lamellar Corneal Flap
Ophthalmology
June’s issue

Since it is a known fact that thinner corneas yield lower IOP measurements and thicker corneas yield higher IOP measurements, Chang and Stulting embarked on a review of 8,113 eyes that underwent myopic LASIK to determine the relationship between IOP readings after LASIK and the amount of refractive correction.

They performed a linear regression analysis of measured IOP change as a function of refractive change, also reviewing age and preop keratometry using multiple regression analyses.

Results indicate that the postop measured IOP decreased linearly with the amount of refractive correction and decreased independently as a result of the lamellar corneal flap.

The investigators conclude that the lamellar corneal flap makes no contribution to the load-bearing characteristics of the post-LASIK cornea. Reduction of the measured IOP after corneal refractive surgery has potential implications for monitoring patients for glaucoma. Further prospective studies would help provide insight into the effect of corneal and flap thickness and change in IOP following LASIK and PRK.

Reviews

Reducing Corneal Astigmatism at the Time of Cataract Surgery
American Journal of Ophthalmology
2005:139:767–776

Several procedures have been recommended to reduce preexisting corneal astigmatism at the time of cataract surgery.

Tejedor et al. investigated the best location for the clear corneal incision during phacoemulsification cataract surgery based on the corneal astigmatism.

This randomized noncomparative interventinal case series involved 574 patients. The researchers investigated: 1) the best location (superior or temporal) when there is negligible preexisting corneal astigmatism (n = 89); 2) the amount of astigmatism required in a superior incision for an astigmatic neutral or functional result (n = 141); 3) the effect of associating a relaxing corneal incision perpendicular to the superior incision (n = 102); 4) the comparative effect of nasal and temporal incision and the amount of astigmatism adequate for each alternative when preferable to a superior incision (n = 156); and 5) the refractive consequences of following the conclusions of current and preceding studies (n = 86). Visual acuity, refraction, biomicroscopy, keratometry and videokeratography (Fourier analysis) were performed before and after phacoemulsification and IOL implantation (3.5-millimeter incision). The main outcomes were the corneal refractive and surface regularity index change between preop and six-month postop examination and visual acuity at six months.

In patients without corneal astigmatism, corneal changes induced were greater in superior than temporal incision. After a superior incision (preop steep axis at 90 degrees), a shift of the axis 90 degrees away was less likely with at least 1.5 D of astigmatism. A perpendicular relaxing limbal incision decreased corneal changes. Nasal incision induced greater corneal change than temporal incision (preop steep axis at 180 degrees). A shift of this axis 90 degrees away was more likely with astigmatism < 0.75 D in temporal incision and < 1.25 D in nasal incision.

The authors recommend a superior incision when there is at least 1.5 D of astigmatism and steep axis at 90 degrees. A temporal incision is recommended with astigmatism < 1.5 D and steep axis at 90 degrees, negligible astigmatism, or astigmatism < 0.75 D and steep axis at 180 degrees. Nasal incision is recommended with at least 0.75 D of astigmatism and steep axis at 180 degrees.

Asymptomatic Clinical Retinal Detachments Might Be Observed
American Journal of Ophthalmology
2005:139:777–779

There remains controversy as to the appropriate approach to a long-standing retinal detachment.

Steven Cohen studied the natural history of asymptomatic, clinical rhegmatogenous retinal detachment in a single observer, prospective, consecutive, observational case series.

Consecutive patients were included who were referred to the author’s clinical practice with rhegmatogenous retinal detachment extending greater than two-disk diameters posterior to the equator. Patients whose eye had an intraocular procedure within the past year or who had a history of symptomatic retinal detachment in the fellow eye were excluded. Eighteen eyes of 16 patients were followed for an average of 46 months. The main outcome measure was progression of asymptomatic retinal detachment to symptomatic retinal detachment.

None of the 18 asymptomatic, clinical rhegmatogenous retinal detachments became symptomatic. The posterior margin of one retinal detachment progressed slightly four months into the study and then stabilized for four years and remained asymptomatic.

The author concludes that at least some asymptomatic, clinical rhegmatogenous retinal detachments can be safely observed for many years.

Two Approaches to Treating Diabetic Macular Edema
American Journal of Ophthalmology
2005:139:795–801

Diabetic macular edema is a difficult condition to treat. Yanyali et al. compared the effectiveness of pars plana vitrectomy and removal of the internal limiting membrane with modified grid laser photocoagulation in diabetic macular edema in a prospective randomized, comparative, interventional study.

There were 24 eyes of 12 patients with bilateral diabetic macular edema evaluated. Pars plana vitrectomy with removal of the internal limiting membrane was performed at random in one eye of 12 patients (ILM group), and a single session of modified grid laser photocoagulation was performed in the fellow eyes (grid group). Main outcome measures were the foveal thickness measured with optical coherence tomography and preop and postop visual acuities. All patients were followed for six months.

In the ILM group, mean foveal thickness was 439.2 micrometers preoperatively and 219.8 µm postoperatively (P = 0.002). In the grid group, mean foveal thickness was 407 µm preoperatively and 378.5 µm postoperatively (P = 0.433). Mean decrease in foveal thickness was found to be 219.4 µm in the ILM group and 28.5 µm in the grid group (P = 0.001).

In the ILM group, best-corrected logMAR visual acuity was 0.75 preoperatively and 0.53 postoperatively (P = 0.006). In the grid group, best-corrected logMAR visual acuity was 0.59 preoperatively and 0.49 postoperatively (P= 0.058).

Visual acuity improved by two or more lines in six eyes (50 percent) in the ILM group and in three eyes (25 percent) in the grid group. Visual acuity remained stable in six eyes (50 percent) in the ILM group and in nine eyes (75 percent) in the grid group.

The authors conclude that, based on this small series, pars plana vitrectomy with removal of the internal limiting membrane appears to be more effective than a single session of modified grid laser photocoagulation in the treatment of diabetic macular edema.

Reduction of Foveal Thickness and Visual Acuity in DME Treated With Intravitreal Triamcinolone
American Journal of Ophthalmology
2005:139:802–806

Many times there is an inconsistency between anatomic and visual results in macular disease.

Larsson et al. evaluated the correlation between improvement in visual acuity and the reduction of foveal thickness after a single intravitreal injection of 4 milligrams of triamcinolone in diabetic macular edema.

In this prospective interventional nonrandomized clinical trial, 24 eyes from patients with diabetic macular edema were treated with an intravitreal injection of 4 mg of triamcinolone acetonide. The main outcome measures were the best-corrected logMAR visual acuity and optical coherence tomography performed at baseline and three months after the treatment.

At baseline the average foveal thickness was 462 µm and at three months 257 µm  (P < 0.0001). The best-corrected logMAR average visual acuity was 60.5 ETDRS letters at baseline compared with 65.5 at three months after the injection (P = 0.0001). There was no correlation between the improvement in visual acuity and the reduction of foveal thickness, but there was a correlation between reduction in foveal thickness and the age of the patients.

A single injection of 4 mg of intravitreal triamcinolone acetonide effectively reduces the foveal thickness in diabetic macular edema and improves visual acuity, but there does not appear to be a strong correlation between the reduction of foveal thickness and the improvement in visual acuity.

Amblyopia Treatment in Children Aged 7 to 17 Years Old
Archives of Ophthalmology
2005:123:437–447

The Pediatric Eye Disease Investigator Group report on a randomized amblyopia trial that involved 507 children aged 7 to 17 years old.

The patients were provided with optimal optical correction and then randomized to a treatment group or an optical correction group. The treatment group had two to six hours per day of prescribed patching combined with near visual activities for all patients plus atropine for 7- to 12-year-olds; the second group had optical correction alone. 

In the 7- to 12-year-olds, 53 percent of the treatment group improved 2 or more lines compared with 25 percent of the optical correction group (P < 0.001). In the 13- to 17-year-olds, a treatment group difference was seen only among patients not previously treated for amblyopia (P = 0.03). Most patients were left with a residual visual acuity deficit.
  
Although the study results indicate that visual acuity can improve when amblyopia is treated in older children, it is not yet known whether visual acuity improvement will be sustained once treatment is discontinued. Therefore, conclusions regarding the long-term benefit of treatment and the development of treatment recommendations for amblyopia in this age group await the results of a follow-up study that the PEDIG researchers are conducting on the patients who responded to treatment.

Researchers Identify a TIMP-3 Mutation Associated With Sorsby Fundus Dystrophy
Archives of Ophthalmology
2005:123:542–543

Barbazetto et al. describe a novel TIMP-3 mutation segregating with Sorsby Fundus Dystrophy in a family of Eastern European–Jewish ancestry.

The researchers identified a single base pair change, 508A>T, in the C-terminal domain of the TIMP-3 gene, resulting in a previously undescribed missense mutation, S170C. Affected family members became symptomatic in their third and fourth decades of life with night blindness and visual disturbances subsequently developing into choroidal neovascularization and retinal pigment epithelium atrophy.

In summary, the identification of new disease-causing mutations in inherited retinal diseases, such as Sorsby Fundus Dystrophy, provides a broader understanding of the underlying molecular pathogenesis and allows for improved clinical diagnosis, genetic screening and counseling.

OCT Longitudinal Evaluation of Retinal Nerve Fiber Layer Thickness in Glaucoma
Archives of Ophthalmology
2005:123:464–470

Wollstein et al. followed 64 eyes (37 subjects) of glaucoma and glaucoma-suspect patients for a median of 4.7 years. In semiannual clinical examinations, they used both visual field testing and optical coherence tomography to check each eye for progression of glaucoma.

Kaplan-Meier survival analysis demonstrated a higher progression rate by OCT than by visual field testing. In 22 percent of eyes, OCT indicated progression but visual field testing didn’t; in 9 percent of eyes, visual field mean deviation indicated progression but OCT didn’t; and in 3 percent of eyes OCT and visual field testing both indicated progression. The researchers found that 66 percent of eyes were stable throughout follow-up.

In summary, a greater likelihood of glaucomatous progression was found with OCT compared with visual field testing. This might reflect either false positive readings of the OCT or true damage identified by OCT before detection by conventional methods.

Roundup of Other Journals

Noninvasive Identification of Early Coronary Artery Disease
Journal of the American College of Cardiology
2004:44:2137–2141

Reactive hyperemia peripheral arterial tonometry (RH-PAT) is a noninvasive technique to assess peripheral microvascular endothelial function by measuring changes in digital pulse volume during reactive hyperemia.

Bonetti et al. have shown that this RH-PAT technique may prove to be a useful tool in detecting the early stages of coronary artery disease, since coronary endothelial dysfunction represents an early stage of atherosclerosis.

Using RH-PAT as a measurement tool, they demonstrated that patients with coronary microvascular endothelial dysfunction had a lower peripheral hyperemic response than those with normal coronary endothelial function. Specifically, the RH-PAT index—a measure of reactive hyperemia—was calculated as the ratio of the digital pulse volume during reactive hyperemia divided by that at baseline.

The average RH-PAT index was lower in patients with coronary endothelial dysfunction compared with those who had normal coronary endothelial function. This suggests that RH-PAT may have a role in identifying patients with this disorder.

Cocaine and Phenylephrine Eye Drops as a Possible Marker for Diagnosing Parkinson’s Disease
Journal of the American Medical Association
2005;293:932–934

Can sympathetic dysfunction in the pupils be used as a possible diagnostic marker for Parkinson’s disease? 

Sawada et al. attempted to prove this hypothesis by comparing responses to cocaine eye drops and phenylephrine eye drops. Their hypothesis is based on recent studies showing that—through the use of iodine 123-metaiodobenzylguanidine (MIBG)—cardiac sympathetic innervation is reduced in patients with Parkinson’s.

Cocaine blocks norepinephrine uptake, and cocaine-induced mydriasis is dependent on the sympathetic nerve terminal density. On the other hand, phenylephrine acts directly on the adrenergic receptor to cause mydriasis. This study, published as a research letter to the editor of JAMA, involved 38 patients with Parkinson’s and 20 age-matched controls.

Results indicated that the differences between phenylephrine- and cocaine-induced mydriasis were significantly correlated with the reduction of MIBG cardiac accumulation in patients with Parkinson’s—thus demonstrating reasonable diagnostic accuracy.

While these results must be replicated, the authors conclude that using phenylephrine- and cocaine-induced mydriasis as a marker of systemic reduction of sympathetic innervation may prove of value in diagnosing Parkinson’s.

Measuring Ocular Rigidity in Living Human Eyes
Investigative Ophthalmology and Visual Science
2005;45:409–414

According to Pallikaris et al., the most commonly used pressure-volume relationship to calculate ocular rigidity has been Friedenwald’s equation.

However, this measurement must be performed on enucleated eyes. Other approaches have used direct manometric measurements of living eyes in situ, but these complex calculations present difficulties when applied in daily clinical practice.

The researchers took a different tack, determining the pressure-volume relationship and ocular rigidity coefficient in 79 eyes undergoing cataract surgery. They injected 200 microliters of saline solution—in steps of 4.5 µL—through the limbus into the anterior chamber, while continually monitoring the IOP with a transducer, up to the limit of 66 mmHg. Data within an IOP range of 10 to 35 mmHg were used to calculate the scleral rigidity coefficient.

They found a positive correlation between ocular rigidity and the age of the patients. These ocular rigidity measurements may be of clinical significance when assessing IOP, ocular pulsation, blood flow, effect of topical medications and postrefractive surgery complications. The authors call for future studies to better describe the clinical impact of ocular rigidity.

Thick Acellular Human Dermis for Lower Eyelid Reconstruction
Archives of Facial Plastic Surgery
2005;7:38–44

AlloDerm is an acellular dermal matrix derived from human cadaveric dermis. The tissue is enzymatically processed to remove immunologically responsive cells in the dermis and epidermis, leaving an acellular collagen framework with one basement membrane surface and one dermal surface.

Taban et al. used “thick” AlloDerm grafts (a newer form of the dermal matrix) during lower eyelid reconstruction of patients who had undergone previous lower eyelid blepharoplasty with resultant middle lamellae tethering. They demonstrated long-lasting improvement of lower eyelid position using the thick AlloDerm grafts. Surgical correction also included subperiosteal midface-lift and middle lamellae scar lysis.

While the authors note that thick AlloDerm appears to be a “viable” alternative to hard palate grafts and even thin AlloDerm grafts in repairing lower eyelid retraction, some patients may regard AlloDerm as unacceptable because of possible infectious risks associated with implantation, specifically the possibility of prion-related conditions such as Creutzfeld-Jacob disease.

Consequently, surgeons must discuss risks and benefits of each material with the patient, taking into consideration not only surgical outcome but also patient preferences.




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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