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New Findings from Ophthalmology, AJO and Archives
October’s American Journal of Ophthalmology:
September’s Archives of Ophthalmology:
Roundup of Other Journals:
According to a study by Haller et al., treatment with the dexamethasone (DEX) intravitreal implant 0.7 mg at a six-month interval is safe and tolerable over 12 months in patients with macular edema due to branch retinal vein occlusion or central retinal vein occlusion.
Although this was chiefly a safety investigation, efficacy analyses indicated that improvements in BCVA and central retinal thickness after the re-treatment at six months were similar to improvements seen after the first treatment. However, cataract progression did appear to increase after the second DEX implant. Of note: Treatment-related adverse events such as vitreous hemorrhage, endophthalmitis and retinal detachment were extremely rare both after the first injection and the reinjection.
The researchers conducted two identical prospective studies involving a total of 1,256 patients. The studies consisted of a six-month, randomized, sham-controlled phase followed by a six-month open-label extension. At 180 days, patients were eligible to receive a DEX implant if their BCVA was less than 84 letters or retinal thickness was greater than 250 µm. The DEX implant doses included 0.7 mg and 0.35 mg. Patients randomized to initial treatment with either dose of dexamethasone experienced better visual outcomes than those who received sham treatment.
A 10-year study by Shalchi et al. has documented the highest levels of gram-negative keratitis in any known retrospective survey to date and points to a trend of increasing gram-negative infection. The authors see a link between their findings and the significant rise in soft contact lens wear in the United Kingdom throughout the last 30 years; currently, 3.5 million people in that country (5 percent of the population) wear such lenses, and the most prevalent risk factor for microbial keratitis is contact lens use.
During the 10-year study period extending to December 2008, 476 corneal scrapings were taken and cultured from 440 patients. Culture was positive in 163 samples (34.2 percent), growing 172 organisms. In vitro testing showed widespread gram-negative resistance to chloramphenicol (74.1 percent), with declining sensitivity over the 10-year study. There was 97.3 percent sensitivity to combination gentamicin and cefuroxime, and 94.4 percent sensitivity to ciprofloxacin. The authors found ciprofloxacin resistance in eight (17 percent) of 47 gram-positive isolates tested, but there was no trend toward increasing resistance.
The investigators do not suggest changing the current treatment protocol—second-generation fluoroquinolone monotherapy—to treat microbial keratitis in the United Kingdom. However, the possibility of increasing resistance should be monitored.
Shields et al. have found that immunosuppressed patients should be carefully observed for conjunctival squamous cell carcinoma (SCC), especially given the rate of tumor recurrence and the aggressive nature of the disease. Their findings suggest that surgical resection combined with topical interferon alpha-2B may reduce the risk for recurrence or the appearance of a new tumor.
In this clinic-based analysis, the researchers evaluated the details of 13 immunosuppressed patients referred with conjunctival SCC. Eight of the 13 had undergone organ transplantation (kidneys, liver, heart and lung), with the interval from transplant to conjunctival SCC ranging from 2.5 to 21 years (mean 7.6 years). Four patients had HIV, and one patient had systemic lupus erythematosus and was receiving long-term corticosteroids.
Invasive and aggressive SCC behavior was seen in all 13 patients, with recurrence or new tumor formation in four patients (31 percent). Three patients (23 percent) required exenteration or enucleation, and one patient died as a result of brain invasion by SCC. The remaining five patients were treated with excision and prompt topical interferon alpha-2B, and none showed recurrence or a new tumor.
The authors point out that this aggressive behavior is in contrast to conjunctival SCC in the immunocompetent patient. In these individuals, surgical excision often cures the problem, orbital exenteration is rarely needed and related death is rare.
American Journal of Ophthalmology
Splitting donor corneal tissue for use in separate deep anterior lamellar keratoplasty (DALK) and Descemet membrane endothelial keratoplasty (DMEK) in two recipients within three subsequent days is a safe and effective way to reduce the shortage of donor tissue available for corneal transplantation, Heindl et al. found.
In an interventional case series, the researchers scheduled 50 consecutive eyes with anterior stromal disease suitable for DALK and 50 eyes with endothelial disease suitable for DMEK for split cornea transplantation, performing both procedures within 72 hours.
The researchers found that 47 (94 percent) of the donor corneas could be used successfully for two recipients. In three cases (6 percent), the DALK procedure had to be converted to penetrating keratoplasty (PK), which required a full-thickness corneal graft. As a result, 47 fewer donor corneas were needed to perform 100 surgeries.
Six months after surgery, mean BCVA was 20/36 in the 47 eyes that underwent successful DALK, 20/50 in the three eyes that underwent conversion from DALK to PK, and 20/29 in the 50 eyes that underwent DMEK. Postoperative complications after DALK included Descemet folds in five eyes (11 percent) and epitheliopathy in three eyes (6 percent).
After DMEK, partial graft detachment occurred in 26 eyes (52 percent) and was managed successfully with intracameral air reinjection. All corneas remained clear up to six months after surgery, and no intraocular infections occurred.
Jacobi et al. have provided support to the hypothesis that adult corneal endothelial cells are able to migrate in the human eye and that grafted endothelium migrates onto the host tissue, repopulating the corneal stroma with a regular endothelial phenotype.
In a prospective, observational study, five patients with Fuchs endothelial dystrophy were examined one year after uneventful DMEK. These patients had been selected on the basis of slightly decentered grafts and/or a large descemetorrhexis showing areas of denuded corneal stroma, which were not covered by the patients’ Descemet membrane (DM) or the graft.
These areas were investigated by in vivo confocal laser scanning microscopy, using a specially designed Heidelberg Retina Tomograph II and Rostock cornea module equipped with custom-made software. Source data were used to create large-scale maps of the scanned area in automatic real-time composite mode.
Corneal stroma overlying areas devoid of DM was transparent. In vivo confocal laser scanning microscopy of stroma devoid of DM revealed a monolayer of endothelial cells in all of the patients. The morphologic pattern of these cells was similar to that of endothelial cells on DM grafts but was different from the morphology of the patients’ own endothelium, suggesting migration of donor endothelial cells from DMEK grafts.
LASIK is recognized as an effective procedure for treatment of hyper-opia, but the question of where to center the LASIK treatment is still up for debate. Soler et al. demonstrated that pupil-centered and vertex-centered treatments provide similar visual and optical outcomes but that pupil-centered ablation seems to produce a lower amount of coma and less loss of BCVA in eyes showing large temporal pupil decentration.
In a randomized, double-masked, prospective, single-center trial, 60 eyes of 30 patients with low and moderate hyperopia underwent LASIK. The ablation was centered on the pupil in 30 eyes and on the corneal reflex in the remaining 30 eyes. The outcome measures were the safety and efficacy indices, manifest refraction, UCVA, BCVA and ocular high-order aberrations for a 6-mm pupil size.
At three months postoperatively, the safety index was 0.99 in both the pupil-centered group and vertex-centered group, and the efficacy index and optical aberrations also were similar for both groups. When the researchers considered only those eyes with large pupil decentration, there was a tendency for better visual results in favor of pupil-centered procedures in terms of the safety index and a slight but significant increase of coma in vertex-centered eyes.
Ocular hypertension is not approached by all ophthalmologists in a uniform fashion. Boland et al. found that ophthalmologists were more likely to treat ocular hypertension if they were not glaucoma specialists.
The researchers recruited 118 members of the American Academy of Ophthalmology (AAO) and 58 members of the American Glaucoma Society (AGS). Each physician was first asked how many young and old patients with ocular hypertension he or she would treat to prevent someone from progressing to glaucoma (number needed to treat). The physicians then reviewed 100 simulated cases of patients with ocular hypertension and reported their likelihood of treating each case. Half of these cases were presented with an estimated risk of conversion to glaucoma within five years; the rest were presented without an estimate. The treatment recommendations were analyzed to determine whether subspecialty status or the presence of a risk calculation had any impact on treatment recommendations.
Physicians in both the AAO and AGS groups were more likely to recommend treatment in cases for which a risk calculation was provided, and both groups indicated that they were more likely to treat younger patients. Ophthalmologists who were not glaucoma specialists were more likely than those who were glaucoma specialists to recommend treatment for ocular hypertensive patients.
Archives of Ophthalmology
Lane et al. examined ocular outcomes and survival after proton irradiation in patients who had choroidal melanomas located within one disc diameter of the optic nerve and thus were ineligible for inclusion in the Collaborative Ocular Melanoma Study. The authors found that local control is excellent, survival is not compromised and eye conservation is likely. In many patients, some long-term visual acuity is maintained (count fingers or better).
In this study, radiation complications, visual loss, eye loss, local recurrence and melanoma-related deaths were ascertained in 573 patients who were treated with proton irradiation for peripapillary and parapapillary melanomas between 1985 and 1997 at the Massachusetts Eye and Ear Infirmary. Median follow-up was eight years. Using the Kaplan-Meier method, the researchers estimated cumulative rates of these outcomes and compared them with rates in patients with tumors located farther from the disc (these patients received proton irradiation and were followed during the same period).
Outcomes were similar in the two groups: Cumulative rates of local recurrence were 6 percent in the study group and 4 percent in the comparison group, and melanoma-related mortality rates were 21.3 percent and 23.5 percent, respectively. In the study group, radiation papillopathy developed in 45 percent and radiation maculopathy in 48.2 percent of eyes. Five-year rates of visual loss (worse than 20/200) and enucleation were 79.7 percent and 13.3 percent, respectively. Patients with tumors located more than one disc diameter from the optic nerve experienced better visual outcomes: Visual loss occurred in 39.7 percent, and eye loss occurred in 4.8 percent.
The authors conclude that proton irradiation should be considered for patients who have tumors that are contiguous to the optic disc.
Fan et al. examined the daytime and nighttime differences in aqueous humor dynamics in patients who had ocular hypertension but were not on ocular medication. They found that significant ocular changes occur at night.
Thirty participants with ocular hypertension were enrolled in the study, which included one daytime and one nighttime visit. During each visit, measurements included central corneal thickness, IOP, aqueous flow, outflow facility and blood pressure. Uveoscleral outflow was calculated by the Goldmann equation.
Compared with seated daytime values, notable nighttime changes included a reduction in seated IOP but an increase in supine IOP; a slight but significant thickening of the central cornea; and a decrease in aqueous flow that resulted in slowed outflow through the uveoscleral tissue. Unlike ocular normotensive volunteers from other studies, outflow facility did not decrease at night in the ocular hypertensive patients, probably because daytime values were already low.
In their randomized, controlled, longitudinal study of 48 eyes of 24 patients undergoing unilateral intraocular injections for choroidal neovascularization, Kim and Toma found that repeated exposure of conjunctival flora to ophthalmic antibiotics selects for resistant strains.
Bilateral conjunctival cultures from the injected eye and untreated fellow eye were taken at baseline and after each injection. Patients were randomized to 0.3 percent ofloxacin, 1 percent azithromycin, 0.3 percent gatifloxacin or 0.5 percent moxifloxacin, and they used only their assigned antibiotic throughout the one year of follow-up. Bacterial isolates were tested for antibiotic susceptibility to 16 different antibiotics, and DNA analysis was performed using pulse-field gel electrophoresis. Main outcome measures included changes in antibiotic susceptibility patterns of conjunctival flora after one year.
Coagulase-negative staphylococci (CNS) cultured from eyes repeatedly exposed to fluoroquinolone antibiotics demonstrated significantly increased rates of resistance to both older- and newer-generation fluoroquinolones. In contrast, CNS isolated from eyes exposed to azithromycin demonstrated significantly increased resistance to macrolides. There were also significant increases in multiple-drug resistance observed among CNS isolated from treated eyes.
The authors say that these findings indicate the need for greater caution regarding the use of antibiotics after intraocular injections to reduce the emergence of antimicrobial resistance.
Repka et al. described the structural and visual outcomes of retinal detachments from retinopathy of prematurity (ROP) in 6-year-old children enrolled in the Early Treatment for ROP (ETROP) study. They found that few eyes with retinal detachment from ROP in the study at age 6 retained favorable vision, and then only following repair of stage 4A disease.
The study enrolled 401 children, and retinal detachment occurred in 89 eyes of 63 children. Follow-up data at age 6 were available for 70 eyes (79 percent) of 49 subjects. The retinal detachments were stage 4A in 28 of 70 eyes (40 percent), stage 4B in 14 eyes (20 percent), stage 5 in 13 eyes (19 percent) and not classified in 15 eyes (21 percent).
At age 6, the macula was attached in 17 of 50 eyes (34 percent) following vitrectomy with or without scleral buckle, in six of nine eyes (67 percent) following scleral buckle only and in two of 11 eyes (18 percent) that were observed. Visual acuity was better than 20/200 in six of 70 eyes (8.6 percent); five of the six had stage 4A disease, and one was not classified. Ten stage 5 eyes underwent vitreoretinal surgery; one retained light perception, eight were blind and one could not be tested.
The authors conclude that the data confirm the difficulty of reattaching the retina and obtaining useful vision once the retinal detachment has progressed to include the macula.
Pineles et al. examined a group of patients with type 1 Duane’s syndrome who underwent vertical rectus transposition (VRT). The authors characterized those who required subsequent ipsilateral medial rectus recession; they also found that, after the second procedure, these patients achieved ocular alignment similar to their VRT-only counterparts.
Forty-nine patients with esotropic Duane’s syndrome underwent augmented VRT over a 10-year period. While 26 patients (53 percent) did not require additional surgical procedures to achieve an acceptable ocular alignment, the remaining 23 (47 percent) required subsequent ipsilateral medial rectus recession. Risk factor analysis demonstrated that, compared with patients who needed VRT alone, those who required subsequent medial rectus recessions had significantly greater amounts of esotropia preoperatively in primary position and in adduction, as well as significantly more restriction to adduction on intraoperative forced duction testing.
Following VRT, those patients who eventually underwent medial rectus recession had significantly more postoperative esotropia and torticollis. However, after the subsequent medial rectus recession, there was no significant difference between the primary position deviations in the two groups, although the medial rectus recession group had significantly less adduction.
The authors conclude that, after medial rectus recession, patients demonstrate many findings similar to those who did not require the subsequent procedure.
Roundup of Other Journals
Schröder et al. have found that preoperative aqueous flare, which reflects the blood-ocular breakdown in rhegmatogenous retinal detachment, represents a major risk factor for proliferative vitreoretinopathy (PVR) redetachment.
Because the laser flare-cell meter provides a rapid and noninvasive method to measure the protein content in the anterior chamber, it may serve as a valuable tool to help surgeons identify those patients who could potentially benefit from intravitreal drugs to prevent PVR.
Using a laser flare-cell meter, the researchers measured the aqueous flare of 116 consecutive patients with retinal detachment. The control eyes included 74 partner eyes and 41 eyes of age-matched patients. After at least six months, the investigators followed up with the participants to determine whether another surgery was performed because of PVR redetachment. They found that the 12 patients who developed subsequent PVR redetachment experienced higher flare values than eyes with uncomplicated retinal detachments. In eyes with flare values exceeding 15 photon counts per millisecond, the odds of PVR redetachment development increased 16-fold.
A three-year European study by Bull et al. has shown canaloplasty to be safe and effective, demonstrating significant and sustained reductions in IOP with a favorable risk profile that matches the risks associated with nonpenetrating procedures. Canaloplasty eliminates the need for a subconjunctival filtering bleb and restores the natural trabeculo-canalicular outflow system by means of circumferentially catheterizing, viscodilating and suture-tensioning the entire length of Schlemm’s canal with a flexible microcatheter.
The prospective, multicenter, interventional study involved 109 eyes of 109 patients with open-angle glaucoma undergoing canaloplasty or a combined cataract-canaloplasty procedure. The eyes with canaloplasty had a mean baseline IOP of 23 ± 4.3 mmHg, which decreased to a mean IOP of 15.1 ± 3.1 mmHg three years after surgery. The eyes that underwent the combined cataract-canaloplasty procedure had a mean baseline IOP of 24.3 ± 6 mmHg, which decreased to a mean IOP of 13.8 ± 3.2 mmHg during that time period.
In addition, medication use decreased significantly in both groups. Late postoperative complications included cataracts (19.1 percent) and transient IOP elevation (1.8 percent).
Kránitz et al. have shown that the femtosecond laser can create more precise capsulotomy sizing and centering than manual continuous curvilinear capsulorrhexis (CCC). With the advent of presbyopia-correcting IOLs, which require greater exactness and predictability than monofocal lenses, potential advantages of a precisely controlled femtosecond capsulotomy procedure include prevention of optic decentration.
The investigators performed femotosecond capsulotomies and CCC in 20 eyes of 20 patients. They measured IOL decentration, circularity, vertical and horizontal diameters of capsulotomies and capsule overlap at one week, one month and one year following the procedures. They found that IOL decentration was six times more likely to occur when the capsulorrhexis was performed manually.
The investigators point out that the properly sized, shaped and centered femtosecond capsulotomies resulted in better overlap parameters, thus helping the IOL remain in proper position.