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February 2005

 
Journal Highlights
New Findings from Ophthalmology, AJO and Archives
 
 

March’s Ophthalmology:

Simultaneous Keratoplasty May Be Unnecessary for Cataract Patients With Fuchs’ Corneal Dystrophy

Investigators Study Treatments for Low-IOP Glaucoma Patients

Patient Presents With Eye Infection Caused by Zoonotic Onchocerca

Study Finds That Individuals With AMD Are Less Likely to Use Cholesterol-Lowering Drugs

Appositional Angle Closure Is Observed in Eyes With Shallow Peripheral Anterior Chambers

February's American Journal of Ophthalmology:

Ocular Higher-Order Aberrations in Eyes With Supernormal Vision

The Use of Topical Mitomycin C to Treat Primary Acquired Melanosis With Atypia

A New Option of Primary Placement of a Hydroxyapatite-Coated Sleeve in Bioceramic Orbital Implants

The Effect of Autologous Serum Eyedrops in the Treatment of Severe Dry Eye Disease

December's Archives:

The Pathogenic Implications of Subretinal Gas Migration

A Comparison of Two Treatments for Symptomatic Convergence Insufficiency in Children

Penetration Pharmacokinetics of Topically Administered 5 Percent Moxifloxacin in Humans

Study Examines the Roles of VEGF and SDF-1 in the Pathogenesis of Diabetic Retinopathy

Viscocanalostomy in Monkeys

Roundup of Other Journals:

For Scleritis Patients, Smoking Delays the Response to Treatment

Ocular Tissue Images With Ultrahigh-Resolution OCT

Conjunctival Autograft in Pterygium Surgery: Analysis Over 14 Years


Previews

Simultaneous Keratoplasty May Be Unnecessary for Cataract Patients With Fuchs’ Corneal Dystrophy Ophthalmologys
Ophthalmology
March’s issue

Findings from a study by Seitzman et al. indicate that cataract surgery recommendations in selected patients with Fuchs’ corneal dystrophy may be safely and effectively expanded to exclude simultaneous keratoplasty.

Current practice for these patients includes an initial triple procedure that combines penetrating keratoplasty, cataract extraction and IOL placement. However, a 12-year retrospective experience of 136 patients with Fuchs’ dystrophy showed that a majority with preoperative pachymetry measurements > 600 micrometers maintained excellent visual rehabilitation with cataract surgery alone and did not require penetrating keratoplasty within the first year after cataract surgery.

The authors attribute these findings to the fact that instruments and cataract surgical techniques are continuously improving, with safer small-incision phacoemulsification techniques that are less damaging to the corneal endothelium. While a prospective study is necessary to validate these findings, the authors conclude that changing current guidelines may help avoid the unnecessary cost and delay in visual rehabilitation associated with the initial triple procedure.

Investigators Study Treatments for Low-IOP Glaucoma Patients
Ophthalmology
March’s issue

The Low-pressure Glaucoma Treatment Study by Krupin et al. is the first large (13 centers), double-masked clinical trial comparing the course of low-pressure glaucoma patients randomized to IOP reduction with topical twice-daily brimonidine tartrate 0.2 percent vs. twice-daily timolol maleate 0.5 percent.

Recruitment efforts between 1998 and 2000 identified 190 low-pressure glaucoma patients 30 years or older. Those with an untreated pressure > 21 mmHg with advanced visual field loss were excluded from the study.

Baseline patient characteristics of note included a preponderance of females (59.5 percent), unilateral field loss in 27.9 percent of the participants and frequent optic disc hemorrhage. The central corneal thickness had a normal distribution and did not account for false low pressure measurements.

The authors express optimism that results from this study will help them formulate better treatment alternatives for open-angle glaucoma patients with IOPs at the lower end of the disease spectrum.

Patient Presents With Eye Infection Caused by Zoonotic Onchocerca
Ophthalmology
March’s issue

A case study by Sallo et al. highlights the role of animal filariae in causing human eye infections.

The authors presented a 65-year-old male from western Hungary who complained of rapidly progressive peripheral visual field loss and the sensation of an actively moving object in his central visual field.

Slit-lamp biomicroscopy revealed a thin filariform object surrounded by an opaque transparent “coat” in the anterior vitreous cavity just behind the posterior lens capsule. They observed irregular, spontaneous coiling and thrashing movements, which intensified in the direct light of the slit lamp. The live nematode—identified as an immature filaria, most likely a member of the genus Onchocerca—was removed by pars plana vitrectomy.

The authors note that a worm entering the eye is quite unusual since members of the genus usually inhabit dense connective tissue of their definitive hosts. The findings suggest that with Onchocerca infections apparently on the increase, small worms recovered from the eye cannot arbitrarily be classified as Dirofilaria.

Study Finds That Individuals With AMD Are Less Likely to Use Cholesterol-Lowering Drugs
Ophthalmology
March’s issue

Results from a case-control study by McGwin et al. add to the growing body of evidence that cholesterol-lowering medications may reduce the risk of developing AMD.

The objective of this research focused on evaluating the association between the use of cholesterol-lowering medications and the risk of AMD in the Atherosclerosis Risk in Communities study. This large, prospective, population-based, cohort study was conducted in four communities across the United States. It involved 15,792 individuals aged 45 to 65 enrolled between 1987 and 1989.

The researchers identified 871 AMD cases and 11,717 controls. Of the AMD cases, 11 percent used cholesterol-lowering medications compared with 12.3 percent of controls. Individuals with AMD appeared to have a lower frequency of cholesterol-lowering medication use—a relationship that was statistically significant.

In light of these findings and the detrimental impact of AMD on quality of life, the authors assert that a clinical trial on the impact of statins on AMD “should be pursued without delay.” 

Appositional Angle Closure Is Observed in Eyes With Shallow Peripheral Anterior Chambers
Ophthalmology
March’s issue

Asian patients have eyes with a shallow anterior chamber, and the prevalence of angle-closure glaucoma is higher in Asian than in non-Asian patients. It is important to identify patients who are at risk for angle-closure glaucoma before peripheral anterior synechiae develops.

Kunimatsu et al. conducted a cross-sectional study using ultrasonic biomicroscopy to determine the prevalence of appositional angle closure in Japanese patients with a shallow peripheral anterior chamber but no peripheral anterior synechiae.

The researchers found appositional angle closure in at least one quadrant in 57.5 percent of 80 eyes with a narrow angle with no peripheral anterior synechia under normal room light and in 85 percent in the dark. The angle width, evaluated with conventional gonioscopic grading, and the quadrant of the angle were significantly related to the presence of appositional angle closure.

The authors conclude that while appositional angle closure is probably not a rare finding among Japanese patients, more knowledge about appositional angle closure and a shallow iridotrabecular angle should provide a better understanding of the development of peripheral anterior synechia and angle-closure glaucoma.

Reviews

Ocular Higher-Order Aberrations in Eyes With Supernormal Vision
American Journal of Ophthalmology
February’s issue

Wavefront sensing is an emerging technology that assesses the optical properties of the eye in terms of wavefront aberrations.

Levy et al. quantified the ocular higher-order aberrations in eyes with no prior surgery and with supernormal vision, that is, natural uncorrected visual acuity > 20/15. They analyzed the correlation between ocular HOAs and age in these eyes and investigated the correlation of HOAs between right and left eyes.

Ocular HOAs were examined across a naturally dilated pupil with a diameter > 6 millimeters in 70 eyes of 35 subjects with > 20/15 UCVA (mean age 24.3 years) using the Nidek OPD scan wavefront aberrometer. Root-mean-square values of HOA, total spherical aberration, total coma and total trefoil were analyzed. Correlation analysis was performed to assess the association between monocular HOAs and age and the correlation of HOAs between right and left eyes.

The mean of the root-mean-square values was 0.334 for HOA, 0.110 for total spherical aberration, 0.136 for total coma and 0.268 for total trefoil. There were no significant differences in the mean values of HOA, total spherical aberration, total coma and total trefoil between right and left eyes. The Pearson correlation coefficient between right and left eyes for total spherical aberration was 0.764 (P < 0.0001). No significant correlation was found between right and left eyes for HOA, total coma and total trefoil. No significant correlation was found between each of the ocular aberrations (HOA, total spherical aberration, total coma and total trefoil) and age.

The authors conclude that the amount of ocular HOAs in eyes with natural supernormal vision is not negligible, and its magnitude is comparable to those of reported values of myopic eyes including those before refractive surgery. They propose reassessment of the clinical significance of HOAs and their role in laser refractive surgery. Drs. Pepose and Applegate detail the significance of this manuscript and the wavefront sensing in the “Perspective” section of the same issue.

The Use of Topical Mitomycin C to Treat Primary Acquired Melanosis With Atypia
American Journal of Ophthalmology
February’s issue

There are many forms of therapy recommended for conjunctival primary acquired melanosis with atypia.

Pe’er and Frucht-Pery report the results of 12 consecutive patients with conjunctival PAM with atypia in one of their eyes who were treated by topical mitomycin C in a retrospective interventional consecutive case series.

Eyes with histologically proven PAM with atypia were treated by two to five courses of 0.04 percent (0.4 milligrams per milliliter) topical MMC four times a day. Each course lasted two continuous weeks. Follow-up was conducted on patients for control of local disease, side effects and visual acuity in the treated eye.

In all patients, there was complete or partial response to treatment. In four patients, the pigmentation disappeared, while in eight patients, some remnants of the pigmentation remained. In seven of these eight patients, the remnants of the pigmentation were stable during the follow-up period of four months to nine years, while one in whom they detected regrowth of the PAM was re-treated by topical MMC successfully. No patients lost visual acuity at the end of the follow-up. All side effects of the local chemotherapy were resolved after cessation of the treatment.

Topical MMC chemotherapy seems to be a good alternative to surgical excision and cryotherapy in treating conjunctival PAM with atypia. Dr. Devron Char provides a critical appraisal of this treatment in AJO’s “Editorials” section.

A New Option of Primary Placement of a Hydroxyapatite-Coated Sleeve in Bioceramic Orbital Implants
American Journal of Ophthalmology
February’s issue

Hydroxyapatite orbital implants are commonly used during enucleation, evisceration and secondary orbital implant surgery.

Liao et al. report on a new surgical option of primary placement of a hydroxyapatite-coated sleeve into the bioceramic implant during enucleation or evisceration in a retrospective, observational case series.

A standard enucleation or evisceration was performed, followed by the preplacement of a hydroxyapatite-coated sleeve into the bioceramic implant. Care was taken to ensure the sleeve had been positioned centrally when the implant was placed inside the orbital socket.

Twenty-seven patients were treated with five enucleation and 22 evisceration procedures. Five of the sleeves were exposed spontaneously during one to four months after the original surgery. There were no further complications, except for one sleeve around which there were visible bioceramic spicules attributable to long-term corticosteroid usage.

The 22 sleeves that did not spontaneously expose pursued secondary exposure of the sleeve and peg insertion by the conjunctival cutdown procedure three months postoperatively. One sleeve was medially positioned far away from the implant center. Reinsertion of new sleeve and peg was scheduled two weeks later. One additional sleeve was obliquely positioned after conjunctival cutdown procedure. All 27 patients were successfully fitted with a peg-coupled prosthesis with good motility.

Primary placement of a hydroxyapatite-coated sleeve into the bioceramic implant has several advantages including high patient acceptance, technical simplicity and office-based conjunctival cutdown pegging procedure. By avoiding the expense of postoperative imaging studies and additional prosthetic modification, a more rapid and efficient rehabilitation is possible. Dr. David Jordan provides a critical appraisal of this technique in the “Editorials” section of the same issue.

The Effect of Autologous Serum Eyedrops in the Treatment of Severe Dry Eye Disease
American Journal of Ophthalmology
February’s issue

Conventional therapies for dry eye are frequently unsuccessful in providing patient relief consistently.

In a prospective randomized case-control study, Kojima et al. evaluated the effectiveness of the autologous serum eyedrops in the treatment of severe dry eye patients.

Twenty patients (37 eyes) with severe dry eye without punctal occlusion were enrolled in this study. After two weeks of washout, they were randomly assigned to two groups. One group of patients used only preservative-free artificial tears, and the other group of patients used only autologous serum eyedrops. The authors evaluated the results of a Schirmer test, fluorescein and rose bengal staining scores, tear film breakup time and subjective symptom scores before and two weeks after treatment.

The mean tear film breakup time and fluorescein and rose bengal staining scores, as well as subjective symptom scores, showed significant improvement in the patients assigned to autologous serum eyedrops compared with subjects assigned to preservative-free artificial tears after two weeks of treatment.

Autologous serum eyedrops were found effective in the treatment of severe dry eye disease as evidenced by improvement of tear stability and ocular surface vital staining scores.

The Pathogenic Implications of Subretinal Gas Migration
Archhives of Ophthalmology
2004;122:1793–1800

Johnson et al. reviewed the medical records of four patients with atypical optic nerve coloboma or large optic pit who developed subretinal gas migration after vitrectomy for macular detachment.

Migration of gas or silicone oil was noted intraoperatively in one case and first appeared between one and 17 days in the remaining cases. Theoretical calculations showed that the pressure differential required for the migration of gas through a small defect in the roof of a cavitary disc lesion is well within the range of expected fluctuations in cerebrospinal fluid pressure. A smaller pressure gradient is required for migration of silicone oil or heavy liquids, suggesting that these tamponading agents should probably be avoided in such cases.

In summary, these observations provide clinical confirmation of a defect in tissue overlying cavitary optic disc anomalies and imply interconnections between the vitreous cavity, subarachnoid space and subretinal space. The authors theorize that intermittent pressure gradients resulting from normal variations in intracranial pressure play a critical role in the pathogenesis of retinopathy associated with cavitary disc anomalies. 

A Comparison of Two Treatments for Symptomatic Convergence Insufficiency in Children
Archives of Ophthalmology
2005;123:14–24

In this multicenter randomized clinical trial, Scheiman et al. evaluated the treatment of symptomatic convergence insufficiency in children who were at least 9 but younger than 18 years old.

The researchers randomized 47 patients to one of three treatments: pencil push-ups, vision therapy/ orthoptics or placebo vision therapy/ orthoptics. After 12 weeks of treatment, the children in the vision therapy/ orthoptics group showed a statistically and clinically significant improvement in both the signs and symptoms associated with convergence insufficiency. Pencil push-up treatment was not effective in decreasing either signs or symptoms and was no more effective than placebo vision therapy/orthoptics.

These data indicate that vision therapy/orthoptics is effective in improving both the symptoms and signs associated with convergence insufficiency in children and this cannot be explained on the basis of a placebo effect.

Penetration Pharmacokinetics of Topically Administered 5 Percent Moxifloxacin in Human
Archives of Ophthalmology
2005;123:39–45

In this prospective, nonrandomized study of 20 patients scheduled for vitrectomy surgery, Hariprasad et al. investigated the penetration of moxifloxacin 0.5 percent into the aqueous and vitreous.

Aqueous and vitreous samples were obtained and later analyzed after topically administering moxifloxacin 0.5 percent, either every two hours or every six hours, for three days prior to surgery.

Mean moxifloxacin concentrations in the q2h group for aqueous (n = 9) and vitreous (n = 10) were 2.28 + 1.23 micrograms per milliliter and 0.11 + 0.05 µg/ml, respectively. Mean moxifloxacin concentrations in the q6h group for aqueous (n = 10) and vitreous (n = 9) were 0.88 + 0.88 µg/ml and 0.06 + 0.06 µg/ml, respectively. MIC90 levels were far exceeded in the aqueous for a wide spectrum of key pathogens. Concentration of moxifloxacin in the vitreous did not exceed the MIC90 for several organisms; however, the MIC50 was exceeded in the q2h group for Staphylococcus epidermidis, S. aureus, Streptococcus pneumoniae, Haemophilus influenzae, Bacillus cereus and other gram negatives.

The Endophthalmitis Vitrectomy Study revealed that 94.2 percent of isolates from postoperative endophthalmitis are gram positive. Moxifloxacin has a spectrum of coverage that appropriately encompasses the most common organisms in endophthalmitis, and the pharmacokinetic findings of this investigation reveal that relatively high aqueous levels can be achieved after topical administration. Further studies will help define the precise role of moxifloxacin 0.5 percent ophthalmic solution in the treatment of, or prophylaxis against, intraocular infections.

Study Examines the Roles of VEGF and SDF-1 in the Pathogenesis of Diabetic Retinopathy
Archives of Ophthalmology
2004;122:1801–1808

In a 36-patient, six-month prospective study, Brooks et al. examined the relationship between vitreous levels of the chemokine stromal derived factor-1 and vascular endothelial growth factor.

Vitreous samples were obtained from patients with varying degrees of diabetic retinopathy and diabetic macular edema before and after intraocular injection of triamcinolone acetonide, used to treat refractory diabetic macular edema. Both VEGF and SDF-1 were significantly higher in patients with proliferative diabetic retinopathy than in patients with nonproliferative diabetic retinopathy. SDF-1 levels were markedly increased in patients with diabetic macular edema compared to those without, and VEGF correlated with SDF-1 levels and disease severity. Triamcinolone administration resulted in dramatic reductions of VEGF and SDF-1 to nearly undetectable levels, eliminated diabetic macular edema, and caused regression of active neovascularization.

In summary, this study shows concurrent roles of SDF-1 and VEGF in the pathogenesis of diabetic retinopathy, and suggests that the elimination of diabetic macular edema, after triamcinolone injection, may be due to the suppression of VEGF and SDF-1.

Viscocanalostomy in Monkeys
Archives of Ophthalmology
2004;122:1826–1838

Tamm et al. examined the structural changes and aqueous humor outflow after viscocanalostomy in live normal monkey eyes.

Viscocanalostomy surgery was performed in four rhesus monkeys. Though Schlemm’s canal was replaced by scar tissue at the surgical site, outflow facility (n = 2) increased by approximately 30 percent. The most likely explanations for the facility increase are persisting focal disruptions of the inner wall endothelium of Schlemm’s canal and opening of the juxtacanalicular region, resulting in direct communication of juxtacanalicular region extracellular spaces with the lumen of Schlemm’s canal. The continuous presence of sodium hyaluronate might prevent repair of these defects by interfering with thrombocyte function.

In summary, the viscocanalostomy procedure in nonhuman primates appears to reduce outflow resistance by opening the inner wall endothelium of Schlemm’s canal and the juxtacanalicular region of the trabecular meshwork, areas affected by pathologic change in glaucoma in humans.

Roundup of Other Journals

For Scleritis Patients, Smoking Delays the Response to Treatment
Eye
Advance online publication, Nov. 5, 2004.
(Go to www.nature.com/eye for eye.6701731.)

Yet another study has illustrated potential problems associated with smoking. Boonman et al. have found that in patients with episcleritis or scleritis, smoking delays the full response to therapy by a month or more in many patients—irrespective of the type of medication taken.

Of 103 patients diagnosed with either episcleritis or scleritis, 41 were smoking during treatment of the scleral inflammation, 19 patients had a smoking history and 43 patients had never smoked. Medications included nonsteroidal anti-inflammatory drugs, oral steroids in immunosuppressive doses, and disease-modifying agents. The response to any of the given medications was delayed by at least four weeks in many smoking patients, particularly those with posterior scleritis. Patients over age 48 were even more likely to respond belatedly to therapy.

The authors were not able to determine whether those who smoke should be treated more aggressively at presentation or whether simply stopping them from smoking during treatment would allow the medication to retain its effectiveness.

Ocular Tissue Images With Ultrahigh-Resolution OCT
Investigative Ophthalmology & Visual Science
2004;45:4126–4131

Grieve et al. have taken optical coherence tomography to a new level. The investigators used an ultrahigh-resolution, full-field (rather than spot) OCT in an attempt to explore the capabilities of the technique on ocular tissues ex vivo. They found that this system, which uses a Linnik-type interferometer with a tungsten-halogen source, was capable of cellular-level imaging of unstained ocular tissues with high penetration depth. For example, the penetration of full-field OCT was sufficient to image an arteriovenous crossing, and in the optic nerve, the convergence of axons and vessels was visible.

The 3-D data set offered the possibility of combining en face and cross-sectional images to provide complementary information—revealing structures that pass unseen in the cross-section and vice versa.

The authors conclude that the relative technical simplicity of this technique holds potential for adaptation to in vivo conditions and suggested imaging ex vivo human eyes obtained from an eye bank to further explore the capabilities of this technology.

Conjunctival Autograft in Pterygium Surgery: Analysis Over 14 Years
Eye
Advance online publication, Oct. 29, 2004.
(Go to www.nature.com/eye and search for eye.6701728.)

According to a study by Fernandes et al., conjunctival autograft with or without amniotic membrane transplantation appears to be the safest and most effective treatment alternative for primary and recurrent pterygia. In contrast, while bare sclera technique is perhaps the quickest and easiest surgical approach, it has an unacceptably high recurrence rate.

The authors conducted a retrospective analysis of medical records of 920 patients (989 eyes) with primary and recurrent pterygia operated between January 1988 and December 2001. Following primary and recurrent unilateral pterygium excision, respectively, recurrences were seen in 19.4 percent and 33.3 percent of eyes after bare sclera technique; 16.7 percent and none after primary closure; 26.7 percent and none with amniotic membrane graft; 12.2 percent and 31.3 percent with conjunctival autograft; and 17.3 percent and 40 percent with conjunctival-limbal autograft. Males, patients under 40 years of age, and those with vascular pterygia faced a greater risk of recurrence.

The authors call for a prospective study to compare conjunctival autograft, conjunctival-limbal autograft and amniotic membrane graft to determine the most effective treatment alternative for primary and recurrent pterygia.

_______________________________
Ophthalmology previews are written by Lori Baker Schena and edited by John Kerrison, MD. American Journal of Ophthalmology summaries are written by Thomas J. Liesegang, MD. Archives 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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News and Views

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