EyeNet Magazine >> Journal Highlights
New Findings From Ophthalmology, AJO and Archives
Bilateral Blindness Uncommon in Patients Treated for Open-Angle Glaucoma After 1975
One-Tenth of LASIK Patients Need Re-treatment in the First Year; Age and Higher Correction Increase Risk
Endocrine Abnormalities Linked to Central Serous Chorioretinopathy
Two-Year Results of Verteporfin in PDT for Myopic Subfoveal CNV Show Continued Visual Benefit
Findings Reported for First U.S. Clinical Series With Deep Lamellar Endothelial Keratoplasty Procedure
Photodynamic Therapy Doesn’t Seem to Lead to Permanent and Complete Occlusion of the CNVM
Indocyanine Green May Adversely Affect the Functional Outcome of Macular Pucker Surgery
Interocular Differences in Corneal Asphericity May Have Implications for Refractive Surgery
Mathematical Model of Corneal Surface Smoothing After LASIK
Gene Expression in Donor Corneal Endothelium
Evaluation of Conjunctival Intraepithelial Neoplasia With High Frequency Ultrasound
Vitritis and Chorioretinitis in a Patient With West Nile Virus
Antioxidant Vitamin Supplements in Postmenopausal Women With Coronary Atherosclerosis
Narrowing of the Optic Canal in Fibrous Dysplasia
Light-Induced Retinal Degeneration
Previews
Bilateral Blindness Uncommon in Patients Treated for Open-Angle Glaucoma After 1975
April’s Ophthalmology
In a retrospective observational study of blindness from open-angle glaucoma, Philip P. Chen found that the Kaplan-Meier estimate at 15 years for the development of unilateral blindness from glaucoma was 14.6 percent and bilateral blindness was 6.4 percent.
This retrospective chart review study included 186 patients diagnosed with open-angle glaucoma in 1975 or later and treated for at least two years for the disease. This time period was selected to include individuals who likely would have benefited from advances in glaucoma management that occurred starting in the late 1970s.
Chen found that development of blindness was significantly associated with both noncompliance with the treatment regimen and worse initial visual field loss. In addition, nonwhite race was associated with blindness when all blindness—including that found at diagnosis—was taken into consideration.
The author concludes that the prognosis for patients diagnosed with open-angle glaucoma in the past 25 years is encouraging since bilateral blindness appears to be uncommon; ongoing prospective studies could help determine if this conclusion is valid.
One-Tenth of LASIK Patients Need Re-treatment in the First Year; Age and Higher Correction Increase Risk
April’s Ophthalmology
Hersh et al. found that 10.5 percent of patients undergoing LASIK require re-treatment of residual visual complaints within one year.
In this retrospective study, the authors looked at the re-treatment rate in 2,485 eyes of 1,306 patients undergoing LASIK by a single surgeon for myopia, hyperopia or astigmatism. They didn’t take into consideration re-treatment for such complications as epithelial ingrowth, flap striae or diffuse lamellar keratitis; rather, they focused on re-treatment for residual refractive error after uncomplicated surgery. During re-treatment, most of the LASIK flaps in the study were lifted using a manual technique described in the report. Three eyes required a repeat microkeratome cut.
In addition to reporting the 10.5 percent re-treatment rate, the investigators discovered that higher initial corrections, astigmatism and being 40 or older are risk factors for LASIK re-treatment. Another observation was that patients treated on the LadarVision laser had almost twice the rate of re-treatment (18.2 percent) compared with the Summit Apex Plus Laser (9.7 percent).
The authors warn that patient expectations in many cases may be greater than LASIK can offer; thus, patients should be given an accurate prediction of their likelihood of needing re-treatment to provide full informed consent.
Endocrine Abnormalities Linked to Central Serous Chorioretinopathy
April’s Ophthalmology
There is a growing body of data—augmented by findings from this study—suggesting that disruption of the hypothalamic-pituitary-adrenal axis is a key physiologic change associated with the development of central serous chorioretinopathy.
In this study, Haimovici et al. found that 50 percent of patients with acute CSCR had elevated 24-hour urine corticosteroids. Steroid levels may contribute to the pathogenesis of the disorder. In addition, 30 percent of patients exhibited disruption of the normal diurnal pattern of cortisol secretion—further evidence of an endocrine disturbance. Another important finding from the study was that nearly one-third of patients had evidence of endogenous mineralocorticoid dysfunction as indicated by 24-hour urine for tetrahydroaldosterone—a newly described attribute of CSCR.
The researchers conclude that endogenous corticosteroid dysfunction may be a central feature in the pathogenesis of CSCR and that the apparent deregulation of the renin-angiotensin-aldosterone system deserves further study.
Two-Year Results of Verteporfin in PDT for Myopic Subfoveal CNV Show Continued Visual Benefit
April’s Ophthalmology
In a trial evaluating photodynamic therapy with verteporfin (Visudyne) in patients with subfoveal choroidal neovascularization caused by pathologic myopia, the two-year results confirmed previous one-year findings suggesting that this treatment approach has a safe visual benefit compared with placebo therapy.
The primary outcome for the original research was the proportion of eyes with fewer than eight letters (approximately 1.5 lines) of visual acuity loss. At one-year follow-up, the primary outcome was statistically significant in favor of verteporfin therapy compared with placebo. However, at two years, while the verteporfin therapy group was more likely to have improved visual acuity than was the placebo group, the primary outcome was not statistically significant.
Nevertheless, given the overall beneficial outcomes favoring the verteporfin- treated group, the Verteporfin in Photodynamic Therapy Study Group recommends this approach in treating subfoveal CNV resulting from pathologic myopia.
Findings Reported for First U.S. Clinical Series With Deep Lamellar Endothelial Keratoplasty Procedure
April’s Ophthalmology
After looking at the six- and 12-month results of the first U.S. clinical series of deep lamellar endothelial keratoplasty in the treatment of endothelial dysfunction, Terry and Ousley et al. report that the technique offers considerable advantages over penetrating keratoplasty. This prospective case series includes eight eyes of eight patients with corneal edema from Fuchs’ dystrophy and pseudophakia.
The investigators found that DLEK, with its absence of corneal surface incisions and sutures, provides a smooth surface topography with minimal astigmatism, a predictable and stable corneal power, a healthy donor corneal endothelium and a tectonically stable globe. The central stromal interface quality was good, but there was room for improvement.
Since DLEK is still in its evolutionary stages, the investigators caution that it should be performed under the auspices of an institutional review board. Future developments will include further refinement of interface creation, and the authors maintain that the procedure holds great potential for becoming the preferred surgical method of endothelial replacement.
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Ophthalmology previews are written by Lori Baker Schena and edited by John Kerrison, MD.
Reviews
Photodynamic Therapy Doesn’t Seem to Lead to Permanent and Complete Occlusion of the CNVM
American Journal of Ophthalmology
2003;135:343–350
In a multicenter retrospective study in the United States, Moshfeghi et al. report the clinicopathologic findings after submacular removal of choroidal neovascular membrane treated by photodynamic therapy with verteporfin (Visudyne).
Eight eyes of eight patients underwent the surgery. One eye had presumed ocular histoplasmosis, three had age-related macular degeneration, two had pathologic myopia, one had punctate inner choroiditis and one had idiopathic CNVM. Membranes were processed and stained with either hematoxylin and eosin or toluidine blue for light microscopic examination. Some sections were examined by transmission electron microscopy.
Histopathologic and ultrastructural examination showed areas of vascular occlusion at three days that were not seen later. All specimens had patent CNVM. There were signs of vascular damage with extravasated erythrocytes and fibrin, pigment clumping in cells and inflammatory cells in all but the three-day specimens. PDT with verteporfin does not appear to lead to permanent and complete occlusion of the CNVM.
The case series presents data only from patients who refused repeat treatment with PDT or who developed submacular hemorrhage after initial PDT. Treatments that lead to permanent closure of the CNVM without damage to the retinal pigment epithelium and sensory retina are still needed.
Indocyanine Green May Adversely Affect the Functional Outcome of Macular Pucker Surgery
American Journal of Ophthalmology
2003;135:328–337
In Germany, Haritoglou et al. compared functional and ultrastructural results after macular pucker surgery either with or without indocyanine green staining of the internal limiting membrane.
Commercially available ICG with a concentration of less than 0.5 percent and an osmolarity of 275 milliosmoles was used to stain the internal limiting membrane.
Functional outcome measures included visual acuity and Goldmann perimetry.
Those patients who had surgery without ICG experienced a significant improvement of median BCVA from 20/63 preoperatively to 20/40 postoperatively (p < 0.001). But median BCVA remained 20/63 before and after ICG-assisted peeling (p > 0.9). An improvement of vision was noted in 86 percent of patients without ICG-assisted surgery and 55 percent of patients with such surgery.
Thirty-five percent of patients after ICG application presented with a deterioration of visual acuity. The authors also observed large visual field defects in seven of 20 patients after staining of the internal limiting membrane.
No visual field defects were noted after conventional peeling.
There was more cellular debris visible in specimens after ICG application during surgery.
Epiretinal cells had ruptured and lost their cellular integrity following ICG-assisted vitrectomy.
ICG-assisted surgery for macular pucker might have an adverse effect on functional outcome. The cause of this effect remains unknown.
Interocular Differences in Corneal Asphericity May Have Implications for Refractive Surgery
American Journal of Ophthalmology
2003;135:279–284
Jiménez et al. from Spain evaluated the impact that interocular differences in corneal asphericity exert on binocular summation measured as the contrast- sensitivity function.
The investigators classified 92 emmetropic subjects into three groups according to the interocular differences in corneal asphericity measured with an EyeSys 2000 corneal topographer. The contrast-sensitivity function was measured monocularly for each eye and binocularly with a B-VAT 2 device.
Although the binocular contrast-sensitivity function for the three groups studied was greater than the monocular in all the spatial frequencies studied, there were significant differences in binocular summation.
The authors conclude that differences in corneal asphericity may affect the binocular visual function by diminishing the binocular contrast-sensitivity function.
This result may have implications in refractive surgery since the patient may become emmetropic, but the induced interocular differences in corneal asphericity may reduce binocular visual performance.
Mathematical Model of Corneal Surface Smoothing After LASIK
American Journal of Ophthalmology
2003;135:267–278
Huang et al. constructed a quantitative model of corneal surface smoothing after LASIK. The theory is derived from differential equations that describe epithelial migration, growth and loss. Computer simulations calculated the effects on postoperative epithelial thickness, topography, refraction and spherical aberration:
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Simulated epithelial remodeling after myopic ablation produces central epithelial thickening, reduction in achieved correction and induction
of oblate spherical aberration.
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Simulation of hyperopic ablation shows peripheral epithelial thickening, a larger reduction in correction and induction of prolate spherical aberration.
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Simulation using a minus cylinder laser ablation pattern shows decreased astigmatism correction and increased hyperopic shift.
In a series of 76 patients (96 eyes) patients with LASIK, linear regression of achieved correction vs. ablation setting in hyperopic and minus cylinder corrections matched model predictions.
The cornea appears to smooth over ablated features smaller than 0.5 millimeters. The model provides an approach for designing ablation patterns that precompensate for the smoothing to improve final outcome.
Gene Expression in Donor Corneal Endothelium
Archives of Ophthalmology
2003;121:252–258
Corneal endothelial gene expression potentially holds the key to better understanding of endothelial metabolism, structure and function.
Gottsch et al. obtained normal human corneas from eye banks, and studied the endothelium with microarray analysis and serial analysis of gene expression (SAGE). While numerous SAGE tags matched known genes, more than 2,500 tags had no known match to publicly available databases. Select corneal endothelium structure components, cell-adhesion proteins and pump-function enzymes were identified and confirmed. However, 21 of the top 100 tags were not matched to known genes.
The authors show that gene expression profiles aid in the understanding of corneal endothelial metabolism, structure and function. Understanding these basic components of endothelium function will allow for better resolution of disease states in the future.
Evaluation of Conjunctival Intraepithelial Neoplasia With High Frequency Ultrasound
Archives of Ophthalmology
2003;121:168–172
Assessment of the clinical extent of conjunctival squamous carcinoma remains challenging. Clinical examinations combined with imaging studies have not been fully accurate in defining the extent of the disease process.
Finger et al. report the use of high frequency B-scan ultrasound (20 and 50 megahertz) and show differing features of the disease process dependent upon the depth and extent of tumor involvement. In a series of 11 patients, ultrasound was able to detect differences in the superficial component of the tumor, in comparison with orbital and/or intraocular involvement.
In summary, through the use of high frequency ultrasound, the authors have shown promise in better delineating the extent of involvement of squamous conjunctival neoplasms.
Vitritis and Chorioretinitis in a Patient With West Nile Virus
Archives of Ophthalmology
2003; 121:205–207
The incidence of West Nile virus infection has dramatically increased in the United States since 1999. It is closely related to the St. Louis encephalitis virus. In most cases, it causes a mild fever, though in some primarily older patients, it leads to encephalitis and/or meningitis.
Parnell et al. report a patient with West Nile virus, who developed floaters, along with vitritis and a form of chorioretinitis. The condition stabilized with administration of topical corticosteroids.
Since this initial report, numerous additional cases of chorioretinitis have been described in patients following West Nile virus infections.
Look for additional reports in the literature very soon, further detailing this entity of West Nile virus chorioretinitis.
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AJO reviews are written by Thomas J. Liesegang, MD. Archives reviews are written by William Mieler, MD.
Round-Up of Other Journals
Antioxidant Vitamin Supplements in Postmenopausal Women With Coronary Atherosclerosis
The Journal of the American Medical Association
2002; 288:2432–2440
Ophthalmologists who prescribe high-dose vitamin supplements to postmenopausal women with age-related macular degeneration should take note of this study by Waters et al. that indicates hormone replacement therapy (HRT) and/or antioxidant vitamin supplements may do more harm than good.
The Women’s Angiographic Vitamin and Estrogen Trial, a randomized, double-blind study, involved 423 postmenopausal women who had at least one 15 percent to 75 percent coronary stenosis at baseline coronary angiography.
The women were randomly assigned to one of four treatments:
- HRT and vitamins C and E (500 milligrams of vitamin C twice daily and 400 International Units of vitamin E twice daily);
- HRT and vitamin placebo;
- HRT placebo and vitamins C and E; or
- HRT placebo and vitamin placebo.
The researchers found that neither HRT nor antioxidant vitamin supplements provided cardiovascular benefit. In fact, potential harm was seen for both treatments. Especially of interest to ophthalmologists: All-cause mortality was higher in women assigned to antioxidant vitamins than in those who received the vitamin placebo.
Given these findings, it may behoove ophthalmologists to carefully consider the possible side effects when prescribing high doses of vitamins C and E for AMD in postmenopausal women who have coronary disease
Narrowing of the Optic Canal in Fibrous Dysplasia
The New England Journal of Medicine
2002; 347:1670–1676
Managing fibrous dysplasia around the optic nerve in patients with normal vision is complex. Will these patients benefit from recommended prophylactic decompression of the optic nerve, based on the assumption that the condition causes a gradual constriction of the optic nerve? Or is it better to simply observe these patients based on the potential postoperative complications, namely blindness?
Lee et al. provide some answers in their study of 38 patients with fibrous dysplasia of the lesser wing of the sphenoid bone.
The patients underwent a detailed neuro-ophthalmologic examination and computed tomography of the face and skull, reformatted to measure the extent of involvement of the optic canal and the area of the canals.
The authors found that while encasement of the optic canal in fibrous dysplasia does cause narrowing of the canal, this in and of itself does not result in visual loss.
Consequently, prophylactic decompression of the optic nerve cannot be recommended based on the results of the diagnostic imaging alone, since the presence of fibrous dysplasia does not correlate with visual loss. Because the course of the disease is unknown, they conclude that fibrous dysplasia should be managed based on the results of clinical examination, diagnostic imaging and regular observation.
Light-Induced Retinal Degeneration
Nature Genetics
2002;32:215–216 and 254–260
Hao et al. provide evidence that two separate apoptotic pathways—a bright-light pathway and a low-light dependent pathway—mediate light-induced retinal death.
The authors used knockout mice with defects in rhodopsin signaling shut-off to examine the mechanisms of light damage.
The pathway that was initiated depended on the intensity of light. In bright light, apoptosis occurred in a transducin-independent fashion. In low light, a second apoptotic pathway was activated that, in contrast to the first pathway, required transducin.
The investigators conclude that these results support the “equivalent light” hypothesis as one of several mechanisms that lead to retinal degenerative disease.
In the “News & Views” section of the same issue, Jacobson and McInnes question whether modest light exposures threaten normal human visual longevity, and whether ambient light alters the natural history of human retinal disease. They say the findings by Hao et al. should prompt further study on the role of light on the natural history of retinal diseases, including macular degeneration.
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Round-Up is written by Lori Baker Schena, edited by Jose S. Pulido, MD, MS, MBA.
