EyeNet Magazine

Journal Highlights
New Findings from Ophthalmology, AJO and Archives

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June’s Ophthalmology:

June’s American Journal of Ophthalmology:

April’s Archives of Ophthalmology:

Roundup of Other Journals:



Vitrectomy, DME and Retinal Thickening
June’s Ophthalmology

The Diabetic Retinopathy Clinical Research Network has found that performing vitrectomy on patients with diabetic macular edema may reduce retinal thickening.

The primary cohort included 87 eyes with DME, vitreomacular traction, BCVA of 20/63 to 20/400 and retinal central subfield thickness of greater than 300 µm on OCT. Cataract extraction was not performed at the time of vitrectomy. At six months, the median change in visual acuity involved an improvement of three letters with visual acuity improving 10 or more letters in 38 percent of patients and worsening 10 or more letters in 22 percent. Almost half of the patients experienced a reduction in central subfield thickness to less than 250 µm, and most eyes had a reduction of thickening of at least 50 percent. In terms of complications, the researchers reported five eyes with vitreous hemorrhage, seven eyes with elevated IOP, three retinal detachments and one case of endophthalmitis.

The authors call for additional studies to determine whether vitrectomy represents an improvement over current treatment alternatives.

Automated Detection of Diabetic Retinopathy
June’s Ophthalmology

Abràmoff et al. hypothesized that current diabetic retinopathy detection algorithms are close to both the sensitivity and specificity of a single human expert as well as the measurable performance limit.

The authors compared the performance of the algorithm that won the 2009 Retinopathy Online Challenge Competition with the algorithm currently used in EyeCheck—a large computer-aided early diabetic retinopathy detection project. A single retina expert analyzed fundus photographic sets of 16,670 people with diabetes who had not previously been diagnosed with diabetic retinopathy. The outcomes of the two algorithmic detectors were applied separately to the data set and compared. The authors found that the performance of the two algorithmic detectors did not differ and were close to the mathematical limit of detection for this data set.

The authors conclude that diabetic retinopathy algorithms appear to be maturing and further improvements in detection performance cannot be differentiated from best clinical practices because the performance of competitive algorithm development has now reached the human intrareader variability limit.

Antidepressants and Increased Risk of Cataracts
June’s Ophthalmology

In this nested case-control study, Etminan et al. show that use of selective serotonin reuptake inhibitor (SSRI) antidepressants may be associated with an increased risk of cataracts.

The researchers used an administrative data set of Quebec residents who had received a coronary revascularization procedure. Patients diagnosed for cataract were identified and, for each patient, 10 controls were selected and matched to the patient by index date, age and cohort entry. The adjusted rate ratio for cataracts among current users of SSRI antidepressants was 1.15. Fluvoxamine, venlafaxine and paroxetine had the highest risk of cataracts while citalopram, fluoxetine and sertraline posed no risk. The authors suggest that selectivity of 5-HT receptors might be important in the formation of cataracts.

While the study indicates a possible association between SSRI use and an increased cataract risk, the possibility that this observation may be due to the effect of smoking cannot be excluded, as this variable could not be controlled in the study.

Vitamin E and AMD Risk in Women
June’s Ophthalmology

Results from a randomized trial by Christen et al. indicate that 10 years of alternate-day treatment with 600 IU of vitamin E alone has no material beneficial or harmful effect on the occurrence of age-related macular degeneration.

These findings come from the vitamin E component of the Women’s Health Study, a large-scale trial of 39,876 healthy women taking vitamin E and low-dose aspirin and followed for 10 years. Participants were assigned to take vitamin E or placebo on alternate days. After 10 years, 117 cases of AMD were reported in the vitamin E group and 128 cases in the placebo group. In addition, it appears vitamin E had no significant effect on the secondary endpoints of advanced AMD and total AMD with or without vision loss.

The authors conclude that more research is needed to determine whether vitamin E is a component of an antioxidant combination that can help reduce AMD risks, as suggested in the Age-Related Eye Disease Study.

American Journal of Ophthalmology

Glaucoma Valve vs. Single-Plate Implants
June’s AJO

Nassiri et al. report two-year follow-up data of a prospective, randomized study comparing Ahmed valve implantation and Molteno single-plate implantation treatment of refractory glaucoma.

The authors included patients with refractory glaucoma, defined as uncontrolled IOP of more than 21 mmHg despite maximal antiglaucoma medication, previously failed nonseton surgical treatment or a combination thereof. Ninety-two patients were allocated randomly to each of the study groups and underwent implantation of either the Ahmed valve implant or Molteno single-plate implant and were followed for 24 months.

Those who successfully completed the trial (28 in the Molteno group and 29 in the Ahmed group) achieved significantly lower IOP and fewer glaucoma medications but worse visual acuity 24 months after surgery. The Molteno group, compared with the Ahmed group, achieved significantly lower IOPs after the early postoperative period until the end of the study. Both groups maintained visual field during the follow-up. The rate of surgical failure was comparable in both groups. Median survival time was 24 months for both groups. There were no devastating intraoperative or postoperative complications in either group.

Combined Therapy for Polypoidal Choroidal Vasculopathy
June’s AJO

Sato et al. report a retrospective study on the efficacy of photodynamic therapy with verteporfin combined with intravitreal bevacizumab for polypoidal choroidal vasculopathy. The study included 29 treatment-naïve patients with polypoidal choroidal vasculopathy who were followed for 12 months after the first combined therapy. Patients received 1.25 mg of intravitreal bevacizumab one week before photodynamic therapy with verteporfin. The main outcomes measures were visual acuity and the number of required re-treatments.

The mean BCVA level was 0.25 at baseline and 0.31, 0.39, 0.44, 0.44 and 0.45 at one, three, six, nine and 12 months after treatment, respectively. A significant improvement in the mean BCVA was observed at three, six, nine and 12 months after combined therapy. At 12 months, the mean improvement in BCVA from baseline was 2.69 lines. The BCVA improved in 15 eyes (52 percent) by three lines or more, was stable in 13 eyes (45 percent) and decreased in one eye (3 percent) because of a massive subretinal hemorrhage seven months after the first treatment. Eighteen eyes (62 percent) required one combined treatment during follow-up. Polypoidal lesions recurred in six eyes (21 percent). An abnormal branching vascular network persisted in all eyes. The mean number of treatments with combined therapy averaged 1.59. No serious complications developed.

The combined treatment consisting of photodynamic therapy with verteporfin and intravitreal bevacizumab for polypoidal choroidal vasculopathy seemed to be effective for improving visual acuity and reducing re-treatment rates and complications.

CNV in the MARINA and ANCHOR Trials
June’s AJO

Barbazetto et al. investigated whether monthly intravitreal ranibizumab injections are associated with a lower rate of new choroidal neovascularization in fellow eyes of patients with unilateral neovascular age-related macular degeneration. This was a retrospective analysis of data from randomized, controlled clinical trials.

Incidence of new CNV in fellow eyes was calculated at 12 and 24 months from the MARINA and ANCHOR clinical trials based on fluorescein angiographic reading criteria and investigator evaluation. Patients treated with monthly ranibizumab (0.3 and 0.5 mg) were compared with those receiving a sham injection (MARINA) or photodynamic therapy (ANCHOR).

In MARINA, new CNV developed in 20 percent of the 0.3-mg ranibizumab group by 12 months and in 30 percent by 24 months. The conversion rate in the 0.5-mg ranibizumab group was 21 percent and 38 percent by 12 and 24 months, respectively. In the sham group, 26 percent converted by 12 months and 36 percent converted by 24 months.

In ANCHOR, eyes in 16 percent of the 0.3-mg ranibizumab group converted by 12 months and eyes in 24 percent of this group converted by 24 months. The conversion rate in the 0.5-mg ranibizumab group was 24 percent and 35 percent by 12 and 24 months, respectively. In the photo-dynamic therapy group, 25 percent converted by 12 months and 39 percent converted by 24 months. Differences in conversion rates at 12 and 24 months between the 0.3-mg or 0.5-mg ranibiz-umab groups and respective controls (sham or photodynamic therapy) were not statistically significant.

The results do not seem to support the hypothesis that monthly ranibizumab injections reduce the rate of CNV development in untreated fellow eyes.

Archives of Ophthalmology

Donor Risk Factors for Graft Failure
April’s Archives

Patel et al. examined risk factors for graft failure and late endothelial failure in a cohort of 500 consecutive eyes that had received penetrating keratoplasty by one surgeon.

After excluding regrafts and fellow eyes of the same subject, 388 grafts were available for analysis. By 20 years, 83 grafts were known to have failed and the leading cause (31 percent) was late endothelial failure. Forty-one clear grafts were examined at 20 years—which represented 22 percent of the available clear grafts. For the clear grafts at 20 years, donor endothelial cell loss since the preoperative exam was 74 ± 9 percent and six grafts had an endothelial cell density of less than 600 cells/mm2. Lower preoperative endothelial cell density and higher endothelial cell loss at two months increased the risk of late endothelial failure. Univariate analyses showed that donor age was associated with overall graft failure, whereas donor death-to-transplantation time was not. A multivariate analysis indicated that only the recipient’s diagnosis was a risk factor for overall graft failure, with keratoconus having a lower risk of failure than endothelial dysfunction.

The authors conclude that the major risk factor for graft failure after penetrating keratoplasty is the recipient’s diagnosis, whereas donor age appears to be less important. The length of donor preservation does not predict graft failure, but the effect of preservation time on graft failure warrants a formal study to determine whether extended preservation could be a method of expanding the donor pool.

Progression of Type 2 to Type 1 Retinopathy of Prematurity
April’s Archives

Christiansen et al. examined the frequency and timing of progression from type 2 to type 1 retinopathy of prematurity.

Data were analyzed for one randomly selected eye in each child. There were 294 eyes diagnosed with type 2 ROP. Of these, 65 (22.1 percent) progressed to type 1. The mean interval between first diagnosis of type 2 ROP and detection of type 1 ROP was 9 ± 6.6 days. The study protocol required examination of infants who had low-risk prethreshold ROP in one or both eyes at intervals of two to four days for at least two weeks. There were other infants examined at intervals of less than one week for nonprotocol-related reasons.

Overall, there were 217 eyes with type 2 ROP examined at intervals of less than one week. Of these, 25 (11.5 percent) were diagnosed with type 1 ROP in fewer than seven days—most within one to four days. Of 200 eyes that continued to have type 2 disease at the first follow-up exam and underwent a subsequent exam, 24 developed type 1 ROP in less than seven days. While the risk of rapid progression to type 1 ROP was greatest between 33 and 36 weeks postmenstrual age, the risk extended through 44 weeks postmenstrual age; however, such progression was rare after 41 weeks.

The authors conclude that type 1 ROP can be identified with weekly exams in most eyes following initial diagnosis of type 2 ROP. However, a small subset progresses to type 1 ROP in fewer than seven days. Other variables, such as postmenstrual age at onset of disease, play a role in rapid progression from type 2 to type 1 ROP.

Incidence and Clinical Characteristics of Childhood Glaucoma
April’s Archives

Aponte et al. described the incidence and clinical characteristics of childhood glaucoma in Olmsted County, Minn., the first population- based report of this disorder from the United States.

Using the resources of the Rochester Epidemiology Project—a medical record linkage system designed to capture data on any patient-physician encounter in Olmsted County—the authors reviewed the medical records of all Olmsted County residents younger than 20 years of age and meeting diagnostic criteria for glaucoma or glaucoma suspect from Jan. 1, 1965, through Dec. 31, 2004.

Thirty children were diagnosed with glaucoma during the 40-year study period. The age- and sex-adjusted incidence of childhood glaucoma was 2.29 per 100,000 residents under 20 years of age, with the following types and incidences: 19 cases of acquired glaucoma, six secondary and five primary. The birth prevalence of primary congenital glaucoma during the 40-year period was one in 68,254 births or 1.46 per 100,000 births. Twenty-four glaucoma suspects were also identified, yielding an incidence of 1.9 per 100,000 patients under 20 years of age.

The authors conclude that the incidence of childhood glaucoma in this population was 2.29 per 100,000 or one in 43,575 for patients under 20 years of age. Acquired and secondary forms of glaucoma were the most common while congenital and juvenile glaucoma were rare. They also found that the incidence of primary congenital glaucoma was one in 68,254 births, a rate that is lower than that reported in other general populations.

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

Predictive Value of Pressure-to-Depth Ratio
Published online Feb. 19, 2010

A study by Dooley et al. has not only confirmed the predictive value of the pressure-to-depth ratio in IOP reduction following phacoemulsification cataract surgery, but has shown, for the first time, the predictive value of this index when corrected for central corneal thickness (CCT). In addition, this article describes two new indices of preoperative parameters that can predict IOP reduction following cataract surgery.

The study involved 101 nonglaucomatous eyes undergoing cataract surgery that were measured preoperatively and postoperatively for anterior chamber depth (ACD), anterior chamber volume (ACV), anterior chamber angle (ACA), CCT and IOP. The researchers observed a significant increase in ACD, ACV and ACA and a decrease in mean IOP after the surgery. They also found the pressure-to-depth ratio remained positively correlated with IOP reduction after cataract surgery, even when corrected for corneal thickness. In addition, they discovered two novel indices including preoperative IOP/preoperative ACV and preoperative IOP/preoperative ACA.

They conclude that these findings may prove useful for clinicians managing patients with glaucoma or ocular hypertension who need cataract surgery.

Treating Dysphotopsia Symptoms With IOL Exchange
Journal of Cataract and Refractive Surgery

Dysphotopsia is a condition that may occur after posterior chamber IOL implantation. In negative dysphotopsia, certain portions of the retina are blocked from light. Vámosi et al. reviewed the results of patients with severe negative dysphotopsia who were treated with an IOL exchange. They also measured the distance between the iris and the IOL optic, and compared the results with a group of nonsymptomatic pseudophakic patients.

Of the 3,806 cataract procedures performed, five eyes of four patients experienced severe negative dysphotopsia symptoms, and an IOL exchange was performed in three cases. In one case, the secondary IOL was implanted in the reopened capsular bag and the negative dysphotopsia symptoms continued. In the two other cases, the secondary IOL was implanted in the ciliary sulcus and the symptoms resolved. The distance between the iris and the optic was not statistically significantly different between the eyes with and without symptoms of severe negative dysphotopsia. However, the symptoms of severe negative dysphotopsia improved when the IOL exchange actually reduced the iris-IOL distance.

OCT in Patients With Cataract and Glaucoma
Journal of Glaucoma
Published online March 19, 2010

What is the clinical significance of OCT measurements when managing patients who have both glaucoma and cataract? To find out, Mwanza et al. measured peripapillary retinal nerve fiber layer (RNFL) thickness with OCT scans before and after cataract extraction in 45 patients with cataract (23 of whom also had glaucoma). The researchers graded the cataracts according to the Lens Opacification Classification System III (LOCS) and made four key discoveries.

First, after cataract extraction with IOL implantation, both the average signal strength and RNFL thickness measurements significantly increased. Second, when comparing eyes with cataract only to those with cataract and coexisting glaucoma, the researchers did not find a difference in the magnitude of RNFL thickness. Third, a multivariate analysis revealed that the change in average RNFL thickness measurement depended significantly on preoperative signal strength, which in turn was affected only by maximum LOCS scores. Finally, the extent of RNFL thickness changes was not related to IOP lowering.

Recurrent Disk Hemorrhage and Visual Field Progression Rate
Graefe’s Archive for Clinical and Experimental Ophthalmology
Published online Feb. 25, 2010

Beaufort et al. have found that recurrent disc hemorrhage (DH) does not result in a faster rate of visual field loss in patients with glaucoma compared with a single detected DH.

The investigators studied the disc photographs of two groups of patients. Group A involved 72 patients with a single DH in one eye. Group B involved 45 patients who had experienced at least one recurrence in the same eye. The mean number of visual field tests following the initial DH for both groups was 7.9 ± 2.9, spanning a mean of 4.6 ± 2.2 years. There was no significant difference between the two groups in terms of the mean global rate of progression and the number of eyes reaching a progression endpoint. There was a tendency for the recurrent DH eyes to be followed for a longer period of time with a greater number of disc photographs. Finally, the global rates of progression between the two groups were nonsignificant even after adjusting for follow-up time and number of visual field tests.

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

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