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January 2009

Journal Highlights
New Findings from Ophthalmology, AJO and Archives

January’s Ophthalmology:

December’s Ophthalmology:

January’s American Journal of Ophthalmology:

December’s American Journal of Ophthalmology:

November’s Archives of Ophthalmology:

October’s Archives of Ophthalmology:

Roundup of Other Journals:



Usefulness of Tonometers With Calibration Errors
January’s Ophthalmology

The Goldmann applanation tonometer remains the gold standard to measure IOP. Calibration errors do occur with use, but only the manufacturer can reset the error to zero. This may cause problems in practices where resources or accessibility limit timely tonometer recalibration. Sandhu et al. conducted a study to determine whether IOP measurements made by tonometers with known small calibration errors could be adjusted to reflect true IOP, thus allowing continued clinical use if necessary.

The researchers compared a zero-error tonometer and tonometers with known calibration errors ranging to +5 mmHg. They found that while a relationship does exist between calibration error and clinical error in measured IOP, it is not a one-to-one relationship. If a tonometer has a calibration error of less than +3 mmHg, it would not overestimate IOP by more than 2 mmHg—a finding the authors believe may be clinically acceptable in situations where limited resources prevent regular recalibration by the manufacturer.

Ranibizumab Superior in Patients With AMD
January’s Ophthalmology

Brown et al. have found that monthly intravitreal injection of 0.3 mg or 0.5 mg of ranibizumab for 24 months was effective and superior to verteporfin photodynamic therapy in maintaining or improving visual acuity in patients with predominantly classic subfoveal neovascular age-related macular degeneration.

These results represent the culmination of the two-year, phase 3, randomized, double-masked ANCHOR trial. The visual acuity benefit from injection of ranibizumab proved both rapid and sustained. The superiority of ranibizumab to photodynamic therapy was evident one month after starting treatment, increased to a plateau by the end of the first year and then continued through the second year.

The authors conclude that these results constitute a major breakthrough in the treatment of predominantly classic choroidal neovascularization secondary to AMD. A three-year extension study called HORIZON is currently under way in which patient follow-up and re-treatment are flexible and based on individual patient response and investigator discretion.

Sutureless Repair of Orbital Floor and Rim Fractures
January’s Ophthalmology

Acase series of 82 patients (85 eyes) by Lane et al. found that sutureless repair of orbital floor and rim fractures may be a viable alternative to multilayered periosteal and conjunctival closure.

Patients with isolated floor fractures as well as those with more complex orbital fractures were included in the study. The surgical method involved a transconjunctival incision below the tarsus, which provided preseptal access to the inferior orbital rim. The periosteum was then incised for exploration and repair of the orbital floor fractures. Forced ductions were performed after release of entrapped tissue and placement of an orbital floor implant, and the conjunctiva was reapproximated with forceps and draped into the inferior fornix. The operation was associated with a low incidence of postoperative complications—there were no cases of postoperative implant exposure, infection or migration.

Corneal Indentation Effective in Early Acute Angle Closure
January’s Ophthalmology

Masselos et al. found that corneal indentation (CI) represents a rapid, portable and effective method of reducing IOP in patients JournalHighlights NEW FINDINGS FROM OPHTHALMOLOGY, AJO AND ARCHIVES with acute angle closure.

In this report, the authors detailed seven case studies (eight eyes) of patients who underwent CI as part of their early management of acute angle closure. In this series, IOP was significantly reduced with an average reduction of 20.9 mmHg, and three of four patients with severe acute pain reported early resolution of pain following CI. All patients subsequently were treated with laser peripheral iridotomies or lensectomy using phacoemulsification.

The authors conclude that CI relieves the pain caused by the raised IOP. In addition, by reducing corneal edema, the angle can be visualized and a peripheral iridotomy can be performed safely. CI also can be performed in rural settings when access to resources is limited.

Photodynamic Therapy for Choroidal Hemangioma
January’s Ophthalmology

Boixadera et al. demonstrated that using photodynamic therapy with the standard age-related macular degeneration protocol is an effective treatment of symptomatic circumscribed choroidal hemangioma.

The study involved 31 eyes of 31 patients who underwent the standard PDT protocol for AMD. Of these participants, 82.8 percent required one PDT treatment, 13.8 percent required two PDT treatments and 3.4 percent required three PDT treatments to eliminate exudative retinal detachment. Visual acuity increased from a mean of 20/60 to 20/35, with 69 percent of patients experiencing visual recovery. Cystoid macular edema regressed in all cases and exudative macular detachment disappeared in all but two cases. Visual fields demonstrated resolution of central scotomas.

Biomechanical Failure Process in Ectasia
December’s Ophthalmology

Dawson et al. conducted a retrospective, case series to help explain the pathogenesis of the biomechanical failure process that occurs when the cornea becomes ectatic after LASIK or PRK.

The investigators used light microscopy and transmission electron microscopy to examine 13 specimens from 12 patients undergoing corneal transplantation for progressive ectasia after LASIK or PRK. These histopathologic and ultrastructional studies indicated that post-LASIK and post-PRK ectatic corneas experience thinning and loss of rigidity in the postoperative stress-bearing regions of the corneal stroma—the residual stromal bed after LASIK or the entire full-thickness corneal stroma after PRK—due to a reduction in lamellar number and lamellar thinning. A combined two-phase pathophysiologic process involving interlamellar and subsequent interfibrillar slippage may explain this chronic biomechanical failure process, which is classified as interfiber fracture.

The authors conclude that knowing the exact pathway of biomechanical failure may lead to development of preoperative screening tests for ectasia risk or susceptibility.

OCT Retinal Measurements, Visual Acuity Link in AMD
December’s Ophthalmology

In a retrospective, cross-sectional study of 216 patients, Keane et al. used optical coherence tomography to determine the relationship between retinal morphology and visual acuity in patients with neovascular age-related macular degeneration.

The researchers determined that the presence of increased subretinal tissue thickness/volume on OCT was associated with decreased visual acuity in neovascular AMD. In addition, decreased visual acuity was modestly correlated with increased thickness of the neurosensory retina at the foveal center point. No statistically significant association was found between visual acuity and the total volume of subretinal fluid or pigment epithelial detachment. While a relationship between subretinal tissue thickness/volume and decreased visual acuity was identified, the complexity of the disease and the limitations of the OCT could only account for a small degree of the variation in visual acuity.

The investigators conclude the OCT represents a useful clinical tool to manage patients with neovascular AMD. However, stronger correlations between retinal anatomy and visual acuity may require more sophisticated imaging modalities.

Incidence of Pterygium in the Barbados Eye Studies
December’s Ophthalmology

Nemesure et al. have found that the nine-year incidence of pterygium among black participants in the Barbados Eyes Studies is high (11.6 percent). The study involved 1,888 black participants ages 40 to 84 who were free of pterygium at baseline and underwent an ophthalmologic exam after nine years.

In addition to the incidence rate, investigators found that working outdoors increased the risk 1.5-fold. However, having a darker skin complexion and using eyewear for either reading or distance substantially decreased the risk.

These findings confirm the increased risk of developing pterygium in persons who have worked outdoors all of their lives. The authors conclude their results serve as a call to develop strategies to reduce the incidence of pterygium in this and similar populations.

American Journal of Ophthalmology

Late Exposure of the Bioceramic Orbital Implant
January’s AJO

Wang et al. investigated the longterm outcome of the bioceramic orbital implant in a nonrandomized study of 112 patients who received the implant following either enucleation or evisceration.

For primary or secondary enucleation, the implant was wrapped with Vicryl mesh and an anterior patch graft was added. For eviscerations, the unwrapped implant was inserted into the eviscerated globes with posterior sclerotomies and with the corneas preserved. Primary or secondary placement of a sleeve was performed in some patients.

In this study, 108 patients were available for evaluation and had a mean follow-up period of 36 months. Fifty patients (46 percent) received the pegging procedure. Eight of 108 (7 percent) cases of late exposure were identified an average of 21 months after implantation. No cases of implant exposure were identified in the 30 cases of enucleation and eight cases of secondary implant when the implant was wrapped with Vicryl mesh and an anterior scleral cap was used. Eight exposures developed among the 70 eviscerated patients: two without pegging, three with primary placement and three with secondary placement of the sleeve.

The authors conclude that late exposures of bioceramic implants can be found after long-term follow-up and are associated with evisceration, pegging and prior ocular surgeries. Also, the modified wrapping technique seems to prevent exposure following secondary implantation and enucleation.

Accommodative Loss After Retinal Cryotherapy
January’s AJO

Uno et al. investigated the effects of peripheral retinal cryotherapy on accommodative amplitude in patients with retinal lattice degeneration.

The authors studied 92 eyes in 69 patients treated with cryotherapy for lattice degeneration. Pretreatment and posttreatment accommodative amplitudes were measured and acute accommodative loss was calculated from the difference between accommodative amplitudes before treatment and one week after treatment. The authors investigated the time course of accommodative amplitudes; the acute accommodative loss in different age groups as well as in pretreatment accommodative amplitude groups; the influence of cryotherapy spot numbers on accommodative amplitude; and the influence of cryotherapy sites on accommodative amplitude.

No significant difference was noted between pretreatment and posttreatment accommodative amplitudes in the overall subject cohort. Dividing subjects by age revealed significant decreases in accommodative amplitude only among patients in their teens and 20s at one and three weeks after treatment. Accommodative amplitude was lowest among patients in their teens followed by patients in their 20s. Accommodative amplitudes recovered to pretreatment level by six weeks. Acute accommodative loss was greatest in patients in their teens compared with other age groups. A significant correlation was observed between acute accommodative loss and cryotherapy spot numbers.

Juxtascleral Delivery of Anecortave Acetate for POAG
January’s AJO

During treatment for other ocular conditions, anecortave acetate injection has been found to lower IOP—although the mechanism of action is not fully understood. Robin et al. performed a pilot study evaluating the IOPlowering effects of an anterior juxtascleral depot of anecortave acetate in eyes with primary open-angle glaucoma.

Seven eyes of six subjects with primary open-angle glaucoma (all of whom experienced uncontrolled IOP while previously using one or more topical med ications) received 24 mg of anecortave acetate delivered by anterior juxtascleral depot. IOP was assessed at baseline and regularly after treatment for up to 24 months.

Mean IOP before anecortave acetate treatment was 31 mmHg and dropped by 9.5 mmHg within one week after treatment. This IOP reduction was sustained through six months (8.4 ± 5.4 mmHg) and 12 months (9.5 ± 5.7 mmHg) after a single anecortave acetate treatment. The injection process was well tolerated and no eyes experienced any injection-related or drug-related serious adverse events.

The authors conclude that both the anterior juxtascleral depot of a drug and use of anecortave acetate may be promising candidates for IOP reduction in eyes with primary open-angle glaucoma. Further research is required to better establish their efficacy, optimal dosing frequency, mechanism of action and their additive potential to other IOP-lowering therapies.

Polymerase Chain Reaction in the Diagnosis of Uveitis
January’s AJO

Polymerase chain reaction (PCR) analysis strategies have been an important addition to the armamentarium of infectious disease specialists. Harper et al. assessed PCR analysis of intraocular fluid as a test for infectious uveitis of the posterior segment in a representative patient population.

One hundred and thirty-three patients with possible infectious chorioretinitis underwent PCR testing of aqueous or vitreous samples. Four hundred and thirty-three PCR tests of 105 aqueous and 38 vitreous specimens identified 77 of the 95 patients who had a final clinical diagnosis of infectious uveitis (81 percent). PCR analyses for herpes simplex virus, varicella–zoster virus and cytomegalovirus were performed in almost all cases—with fewer tests for toxoplasmosis or Epstein-Barr.

Clinical features associated with positive PCR results were compromised immunity, retinal vascular inflammation, optic nerve involvement and extensive retinitis. Cases sampled within one week of presentation were more likely to have positive PCR results than those sampled later. The predictive value of positive and negative tests was 99 percent and 68 percent, respectively, in this patient group. Alteration in treatment based on PCR and syphilis serologic results led to disease resolution in 25 of 26 patients.

The authors conclude that PCR testing is a useful adjunct in the diagnosis of infectious causes of posterior uveitis. Patients with vascular or optic nerve inflammation, extensive retinitis or compromised immunity are more likely to have positive PCR results and may benefit from PCR testing of aqueous humor.

Comparison of Techniques of Corneal Transplantation for Keratoconus
December’s AJO

Bahar et al. compared the visual outcomes following deep anterior lamellar keratoplasty (DALK), penetrating keratoplasty (PK) and manual top-hat penetrating keratoplasty (TH-PK) in subjects undergoing corneal transplantation for keratoconus.

The study included 50 patients who underwent corneal transplantation for keratoconus: 17 eyes underwent DALK, 20 eyes underwent traditional PK and 13 had TH-PK.

The median BCVA at 12 months’ follow- up was 20/40 in the DALK eyes and 20/30 in the traditional PK and TH-PK eyes. In each of the three groups, the mean final spherical equivalent power was less than –1 D, and the median astigmatism was less than 3.5 D. Complication rates were similar for the three groups, although the DALK group tended toward more complications. Although DALK and TH-PK resulted in significantly shorter time to suture removal, they caused increased levels of higher-order aberrations. Endo thelial cell counts at 12 months were significantly higher in DALK and TH-PK eyes when compared with the traditional PK eyes.

The authors conclude that DALK, PK and TH-PK provide comparable visual outcomes in keratoconus patients. Although DALK and TH-PK induce more higher-order aberrations, they speed up the time to suture removal and provide higher endothelial cell density at one year of follow-up.

Effect of Corneal Light Scatter After PK
December’s AJO

Patel et al. determined the effect of corneal light scatter on vision after penetrating keratoplasty (PK).The study included 61 eyes with clear grafts at 14.6 years after PK, 12 eyes with late endothelial failure at 19.7 years after PK and 41 normal eyes. Backscatter from different depths of the cornea was measured by a custom scatterometer. Intraocular forward light scatter was measured with a stray light meter, while high-contrast visual acuity (HCVA) was measured by the Early Treatment Diabetic Retinopathy Study protocol or Snellen chart. Finally, mesopic and photopic low-contrast visual acuity (LCVA) were measured with a 10 percent contrast chart.

Backscatter from the anterior, middle and posterior thirds of the corneas was higher in clear grafts than in normal eyes and higher in grafts with late endothelial failure than in clear grafts. Corneal stromal backscatter from clear grafts correlated with time after keratoplasty. Forward light scatter was higher in eyes with clear grafts than in normal eyes and higher in eyes with late endothelial failure than in clear grafts. Corneal stromal backscatter from clear grafts correlated with HCVA, mesopic LCVA and photopic LCVA. Forward scatter in eyes with clear grafts correlated with photopic LCVA.

Interferon Alpha-2a Therapy for Behçet’s-Associated Uveitis
December’s AJO

Gueudry et al. evaluated the longterm responsiveness of interferon alpha-2a (IFN alpha-2a) in patients with severe uveitis associated with Behçet’s disease.

The study included 32 patients with sight-threatening uveitis associated with Behçet’s disease who relapsed following treatment with corticosteroids and immunosuppressive agents. IFN alpha-2a was administered subcutaneously (3,000,000 units three times a week).

Control of inflammation was achieved in 28 of 32 patients. Mean observation period of the 28 responder patients was 70.6 months. Median visual acuity improved from 0.52 to 0.33 two years after initiation of IFN alpha-2a therapy. The relapse rate decreased significantly during IFN alpha-2a treatment from 1.68 relapses per patient per year to 0.11. IFN alpha-2a was discontinued in 19 of 28 patients after 32 months of treatment. Mean follow-up after IFN alpha-2a discontinuation was 43 months. After IFN alpha-2a discontinuation, the relapse rate increased from 0.08 relapse per person per year to 0.74.

IFN alpha-2a appears to be efficient and safe for the long-term management of severe uveitis associated with Behçet’s disease. Although long-term remission is possible in some patients, it seems to be mainly a suspensive therapeutic strategy.

Archives of Ophthalmology

Explaining the Fusarium Keratitis Epidemic of 2004–2006
November’s Archives

Bullock et al. investigated the effect of elevated storage temperature on the ability of contact lens solutions to inhibit growth of Fusarium species.

Six contact lens solutions were studied: ReNu with MoistureLoc, ReNu MultiPlus, Complete Moistureplus, AQuify, Clear Care and Opti-Free RepleniSH. Two bottles of each solution were separately stored at room temperature and 60 degrees C for four weeks serially diluted, then tested for their ability to inhibit growth of 11 Fusarium isolates (seven of which were associated with the keratitis epidemic of 2004–2006).

ReNu with MoistureLoc demonstrated the greatest decline in efficacy after storage at 60 degrees C. Regarding the keratitis epidemic isolates only, ReNu with MoistureLoc stored at room temperature allowed Fusarium growth in 27/84 combinations vs. 67/84 combinations when stored at 60 degrees C. In contrast, ReNu MultiPlus and Clear Care did not allow growth in any of the combinations under either storage condition.

The authors conclude that when exposed to prolonged temperature elevation, ReNu with MoistureLoc loses its in vitro fungistatic activity to a much greater extent than other products. Improper temperature control of ReNu with MoistureLoc may have contributed to the worldwide Fusarium keratitis epidemic of 2004–2006.

Vision-Screening Law and Fatality Rates of Older Drivers
November’s Archives

Arecent Florida law requires all drivers aged 80 years and older to pass a vision test before renewing their driver’s licenses. McGwin et al. examined whether this law had an impact on motor vehicle collision fatality rates.

Motor vehicle collision fatality rates for all Florida residents and for drivers aged 80 years and older were compared before and after the visual acuity licensing standard was implemented in January 2004.

From 2001 to 2006, there was a nonsignificant (p = 0.06) increase in motor vehicle collision fatality rates in Florida. In contrast, fatality rates among drivers aged 80 years and older demonstrated a significant downward linear trend (p = 0.01). When comparing pre- and post-law time periods, the fatality rate among drivers of all ages increased by 6 percent. Conversely, fatalities among drivers aged 80 and older decreased significantly, by 17 percent.

Despite little evidence for an association between visual acuity and motor vehicle collision involvement, the results of this study suggest that a vision screening law targeting Floridians aged 80 years and older resulted in a reduction in the motor vehicle collision fatality rate among such drivers.

CYP1B1 and MYOC Mutations and Primary Congenital Glaucoma
October’s Archives

Chen et al. clinically characterized 116 Chinese patients with primary congenital glaucoma and determined the role of CYP1B1 and MYOC mutations in this cohort.

The authors included 116 unrelated patients with primary congenital glaucoma and 120 ethnically matched, unrelated, healthy controls. CYP1B1 and MYOC were amplified from genomic DNA and followed by direct DNA sequencing to identify diseasecausing variants.

Data showed 20 patients had CYP1B1 mutations. Five of these patients had homozygous mutant alleles and four had compound heterozygous mutations. Fourteen of the mutations were novel. Three patients had MYOC mutations—all of which were novel. The role of mutations in CYP1B1 and MYOC varied, depending on the ethnic origin of the patients.

The investigators conclude that patients with primary congenital glaucoma and CYP1B1 mutations tend to have a more severe phenotype than those without mutations. Genetic testing of CYP1B1 mutations may help predict new cases and their prognoses.

Diabetes Mellitus and Visual Impairment
October’s Archives

Zhang et al. examined the prevalence and correlates of visual impairment among U.S. adults with and without diabetes. The authors examined the National Health and Nutrition Examination Surveys from 1999 to 2004. This data included 1,237 adults with diabetes (average age 59) and 11,767 adults without the disease (average age 45). Distance visual acuity was measured before and after optical correction. Participants’ vision was tested while they were wearing their glasses or contact lenses. Their demographic information was also noted.

An estimated 11 percent of American adults with diabetes had some form of visual impairment (3.8 percent uncorrectable, and 7.2 percent correctable), while only 5.9 percent of those without diabetes had some form of visual impairment (1.4 percent uncorrectable, and 4.5 percent correctable). People with diabetes were more likely to have uncorrectable visual impairment than those without diabetes, even after controlling for other selected factors.

The authors conclude that the high prevalence of visual impairment among people with diabetes indicates a need for diverse public health strategies to reduce the burden of both correctable and uncorrectable visual impairment. It is important to identify and pursue ways to increase access to eye care for everyone and to correct visual impairment, where possible, to diminish morbidity and mortality due to impaired vision.

Survival in Patients With Uveal Melanoma
October’s Archives

Virgili et al. evaluated the relative survival of 5,788 patients with uveal melanoma diagnosed between Jan. 1, 1983, and Dec. 31, 1994, with follow-up to 1999. Data were provided by 32 cancer registries in 16 European countries in the framework of the EUROCARE project.

Univariate five-year relative survival and the multivariate relative excess risk of death were reported as measures of the excess hazard due to diagnosis of cancer once the known baseline hazard—mortality in the general population—was taken into account. Overall fiveyear univariate relative survival was 68.9 percent. In multivariate analyses, mortality was stable from 1983 to 1994. Relative excess risk of death was higher in patients aged 75 years or older compared with patients aged 54 years or younger. Relative excess risk of death was also slightly higher in male patients than in female patients. Compared with the United Kingdom, mortality was similar in Nordic areas and was higher in both eastern Europe and other western European areas. Tumors of unspecified ocular location (ICD-9 code, 190.9) showed higher mortality compared with other ocular subsites, suggesting that this code is used for large uveal melanomas.

The authors confirmed previous findings in population-based studies reporting stable five-year relative survival of patients who were diagnosed with uveal melanoma in recent years. A higher mortality in males has been suggested in previous studies and confirmed here as well.

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

Rituximab for Treatment of Neuromyelitis Optica
Archives of Neurology
Published online Sept. 24, 2008

Neuromyelitis optica is a rare, potentially life-threatening inflammatory demyelinating disorder. The condition targets the optic nerves and spinal cord, with 62 percent of patients becoming functionally blind and 50 percent of patients being confined to a wheelchair within five years of diagnosis. In this case series, Jacob et al. treated 25 patients with rituximab, 23 of whom had previously relapsed while taking other medications. The patients, who ranged in age from 7 to 65 years, with a median of 38 years, received infusions of rituximab at median intervals of eight months.

Results showed that at median followup of 19 months, the annualized relapse rate following treatment with rituximab was lower than the rate prior to treatment with rituximab (zero vs. 1.7, respec tively). In addition, disability improved or stabilized in 20 of 25 patients. Two patients died during the follow-up period (one from a brainstem relapse and the other from suspected septicemia). Twenty percent of patients were diagnosed with infections.

The authors conclude that while rituximab treatment is more expensive than generic immunosuppressive drugs, the higher cost may offset the cost of hospitalizations for relapses. In spite of the study’s limitations, the authors believe the data showing reduced frequency of attacks and subsequent alleviation of disability are credible and provide at least anecdotal evidence to help guide physicians in treating neuromyelitis optica.

Retinal Pigment Epithelial Alterations in Retinitis Pigmentosa
Published online Sept. 12, 2008

In retinitis pigmentosa, studies have indicated that marked alterations of the retinal pigment epithelium (RPE) and the photoreceptors are present in areas where retinal function is preserved. Consequently, noninvasive in vivo visualization of RPE alterations may help clinicians chart the course of the disease and measure effectiveness of different treatments.

Kellner et al. compared two different autofluorescence images—melaninrelated near-infrared fundus autofluorescence (NIA) and lipofuscin-related fundus autofluoresence (FAF)—in patients with retinitis pigmentosa to evaluate the usefulness of NIA for diagnostic purposes.

In this study, 33 patients with retinitis pigmentosa underwent FAF and NIA imaging with a confocal scanning laser ophthalmoscope. Differences were detected in the distribution of FAF and NIA abnormalities, indicating different pathophysiologic processes involving the fluorophones lipofuscin and melanin. The authors note that the FAF and NIA alterations seem to be a universal phenomenon in retinitis pigmentosa patients.

While the mechanisms that contribute to NIA alterations are not yet fully understood, the authors conclude that the combined application of FAF and NIA allows clinicians to monitor RPE abnormalities while providing more information on different pathophysiologic aspects of the degenerative process associated with retinitis pigmentosa.

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

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