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New Findings from Ophthalmology, AJO and Archives
February's American Journal of Ophthalmology:
December's Archives of Ophthalmology:
Roundup of Other Journals:
In a study population of 184 patients, Durrani et al. identified eight individuals who had canalicular obstruction due to lichen planus. Bilateral, bicanalicular involvement was seen in seven out of eight lichen patients, with three of those presenting with completely obstructed canaliculi. Surgeons performed primary dacryocystorhinostomy with retrograde canaliculostomy in half the patients, yet all eight patients required secondary placement of Lester Jones canalicular bypass tubes.
The authors conclude that while about 5 percent of canalicular obstructions are lichen-associated, this number will no doubt increase as more practitioners become aware of the disease.
Penetrating keratoplasty in the treatment of keratoconus is designed to achieve a functioning corneal graft with minimal refractive error. Since the use of same-size trephines for the host cornea and for cutting the donor cornea results in a graft that is smaller than the recipient bed, surgeons routinely use a donor trephine that is larger than the recipient trephine to correct the mismatch in size. However, this compensation has been reported to result in an increase in corneal curvature.
Jaycock et al. investigated whether same-size donor and recipient trephines reduced the degree of myopia after penetrating keratoplasty for keratoconus. In a cohort study, they found the use of same-size donor and recipient trephines did not reduce myopia and was associated with a higher incidence of postoperative wound leaks. There also was no difference in corneal graft survival rates between the groups.
Using data from a retrospective review of 223 eyes of 115 patients diagnosed with ocular mucous membrane pemphigoid, also known as ocular cicatricial pemphigoid, Saw et al. reported on the value of a step-up and step-down immunosuppressive strategy for this condition.
In this study, step-up therapy involved dapsone, sulphapyridine, azathioprine, mycophenolate mofetil and cyclophosphamide, depending on the severity of the disease. Owing to an increased risk of bladder carcinoma, treatment with cyclophosphamide is limited to 12 months, so immunosuppression was stepped-down to the less toxic azathioprine, mycophenolate mofetil, methotrexate or dapsone toward the end of the treatment period.
The mycophenolate mofetil appeared to be effective and well-tolerated for moderately active ocular mucous membrane pemphigoid, while combination sulpha-steroid-myelosuppressive agent therapy in a stepladder regimen proved useful to improve disease control. However, the extent to which maximum immunosuppressive therapy can be given is limited by its toxicity, as 29 percent of patients in this study experienced adverse effects.
Findings from the Blue Mountains Eye Study indicate that higher dietary intake of lutein and zeaxanthin reduces the risk of long-term incident age-related macular degeneration, and the study confirmed findings from the Age-Related Eye Disease Study (AREDS) that high zinc intakes (greater than 15.8 mg/day) may offer protection against AMD. A high intake of vegetables was also protective for AMD. In contrast, higher beta-carotene intake was associated with an increased risk of AMD—even after adjusting for smoking status. The Blue Mountains Eye Study cohort numbered 3,654 at baseline in 1992 to 1994, with 2,454 included in the follow-up five and/or 10 years later.
The authors conclude that, given the differences in findings between this cohort in comparison with the AREDS and Rotterdam Study, further research could help clarify the association between dietary antioxidants and the long-term incidence of AMD.
The decision to perform surgery to treat intermittent exotropia is often based on the clinical assessment of control, defined by Hatt et al. as an estimate of the proportion of time the deviation is manifest and the ease of reestablishing fusion after dissociation.
In this case series, the authors used a six-point clinical control scale to assess the presence and degree of any change in control during the course of a day. Based on assessment of interobserver variability, the researchers found that the control scale provided a reliable means of quantifying the level of control at any given point in time. A large proportion of patients experienced variable control over the course of a day.
These data illustrate that assessment of control at a single point in time does not necessarily represent severity of intermittent exotropia. Consequently, treatment alternatives, such as surgery, should not be determined based on a single observation.
American Journal of Ophthalmology
Central corneal thickness has become an important measurement for prognostication in glaucoma as well as being vital in evaluation for refractive surgery. As part of a population-based study in Ghana, Africa, Kim et al. investigated whether there is a systematic difference in CCT measurements using anterior segment optical coherence tomography as compared with ultrasound pachymetry.
Consecutive subjects with clinically normal corneas underwent CCT measurement by both ultrasound and anterior segment OCT. One eye of each subject was randomly selected for analysis. Two measurements were taken and averaged. Agreement and interobserver variability were also analyzed.
One hundred and fifty-five subjects of African ethnicity and an average age of 57 years were included. Measurements by anterior segment OCT and ultrasound were taken a mean of 15 days apart. The mean ultrasound CCT was 525.3 µm compared with 499 µm with anterior segment OCT. Measurements by the two modalities were strongly correlated, and a significant difference was observed between mean ultrasound and anterior segment OCT CCT. The width of the limits of agreement was 28 µm, about 6 percent of the average pachymetry reading. In 50 eyes randomly remeasured with OCT by a second observer, the intraclass correlation coefficient was 0.91.
The authors conclude that there is a reproducible systematic difference between CCT measurements taken with ultrasound and OCT and that measurements acquired by these two modalities are not directly interchangeable in clinical practice.
This PIER study evaluated the efficacy and safety of ranibizumab administered monthly for three months and then quarterly in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration. In this phase 3b trial, the patients had predominantly or minimally classic or occult CNV with no classic lesions. The patients were randomized 1:1:1 to 0.3-mg ranibizumab, 0.5-mg ranibizumab or sham treatment groups.
Mean changes from baseline visual acuity at 12 months were –16.3, –1.6 and –0.2 letters for the sham, 0.3-mg and 0.5-mg groups, respectively. Ranibizumab arrested CNV growth and reduced leakage from CNV. However, the treatment effect declined in the ranibizumab groups during quarterly dosing (e.g., at three months, the mean changes from baseline visual acuity had been gains of 2.9 and 4.3 letters for the 0.3-mg and 0.5-mg doses, respectively). Analyses of mean change from baseline visual acuity at 12 months by baseline age, visual acuity and lesion characteristics were consistent with the overall results. Few serious ocular or nonocular adverse events occurred in any group.
The authors conclude that ranibizumab administered monthly for three months and then quarterly provided significant visual acuity benefit to patients with AMD-related subfoveal CNV and was well-tolerated.
Melles et al. described the results of transplantation of organ- cultured donor Descemet’s membrane carrying autologous corneal endothelium through a 3.5-mm incision. The procedure is tentatively named Descemet’s membrane endothelial keratoplasty, indicated for the management of corneal endothelial disorders.
In this study of 10 patients with Fuchs’ endothelial dystrophy or pseudophakic bullous keratopathy, a 3.5-mm clear corneal tunnel incision was made, the anterior chamber was filled with air and the Descemet’s membrane was stripped from the posterior stroma. A 9-mm diameter Descemet’s membrane was harvested from an organ-cultured donor corneoscleral rim and inserted into a recipient anterior chamber. The donor tissue was gently unfolded, positioned onto the posterior stroma and secured by completely filling the anterior chamber with air for 30 minutes.
At one month, six eyes had a BCVA of 20/40 or better, and three eyes reached 20/20. At six months, the endothelial cell density averaged 2,030 cells/mm2. Three eyes showed a complete detachment of the donor tissue in the early postoperative course that was managed by removal of the transplant and a secondary Descemet’s stripping endothelial keratoplasty procedure.
Descemet’s membrane endothelial keratoplasty may become a preferable technique to manage corneal endothelial disorders as it provides nearly complete visual rehabilitation. The donor tissue required can be prepared from organ-cultured corneoscleral rims that, at present, are not as common in the United States as in Europe and other areas of the world.
In most instances, the cytology of a macular choroidal melanoma is not revealed until the eye is enucleated. Young et al. reported on transscleral, 30-gauge, fine-needle aspiration biopsy (FNAB) for cytology and cytogenetics in eyes with macular choroidal melanoma.
In this case series, 25 eyes underwent transscleral 30-gauge FNAB of macular choroidal melanoma immediately prior to iodine-125 plaque placement. The main outcome measures were FNAB feasibility, cytology, cytogenetic analysis for monosomy 3 and surgical complications.
Transscleral 30-gauge FNAB of choroidal melanoma in the macula was performed in 24 of 25 eyes (96 percent) and was not feasible in one eye owing to insufficient exposure. Biopsy was diagnostic of choroidal melanoma in 17 of 24 eyes (71 percent). Fluorescent in situ hybridization and/or GeneChip 500k NspI Mapping array analysis for monosomy 3 was completed in 16 of 24 eyes (67 percent), revealing monosomy 3 in five eyes and disomy 3 in 11 eyes. Complications included four eyes with retinal perforation that did not require treatment or result in retinal detachment, nine eyes with submacular hemorrhage and five eyes with vitreous hemorrhage that cleared spontaneously within one month.
Transscleral FNAB of macular choroidal melanoma is feasible in most eyes and frequently yields cytogenetic information relevant to prognosis.
Intravitreal bevacizumab has been used recently for the treatment of neovascular age-related macular degeneration without the benefit of long-term results. Bashshur et al. investigated the efficacy of this treatment in a nonrandomized clinical study.
Sixty patients (60 eyes) with subfoveal choroidal neovascular membrane attributable to AMD participated in this study. All lesion types were included except for retinal angiomatous proliferation. In the initial treatment phase, intravitreal bevacizumab (2.5 mg/0.1 ml) was given at baseline, and then two additional monthly injections were given if the macula was not dry on OCT. The criteria for reinjection after the induction phase were presence of new fluid in the macula, increased central retinal thickness of at least 100 µm, loss of at least five letters of vision with increased fluid in the macula, new classic CNV or new macular hemorrhages. Main outcome measure was the proportion of eyes losing fewer than 15 letters of vision after 12 months.
Fifty-one patients completed the 12 months of study. Mean visual acuity improved from 45.7 letters at baseline to 53.1 letters at 12 months, and 47 eyes (92.2 percent) lost less than 15 letters. Mean central retinal thickness decreased from 327.4 µm at baseline to 227.8 µm at 12 months. A mean of 3.4 injections was given over the course of the study, and no ocular or systemic side effects were noted.
The authors conclude that eyes with AMD treated with intravitreal bevacizumab over 12 months had significant anatomical and functional improvement. Archives of Ophthalmology
Archives of Ophthalmology
Of 133 patients who had undergone excision of lacrimal gland pleomorphic adenomas, 72 were followed up for between five and 34 years in this study by Rose et al.
Tumor recurrence did not occur in the 36 patients where the tumor was excised intact. One tumor recurrence occurred among the nine patients who had undergone inadvertent incisional biopsy prior to intact excision, but no recurrence occurred among the four patients with intraoperative spillage of cells during attempted intact excision of the tumor. There were no cases of recurrence in the six patients who had tumor resection after being referred with recurrent disease.
As recurrence after surgically intact excision of lacrimal gland pleomorphic adenoma is rare, the long-term follow-up for patients after excision of these tumors could be reserved for those with known surgical disruption of the tumor pseudocapsule.
Kahana et al. applied a new noninvasive technique of dynamic contrast-enhanced magnetic resonance angiography (MRA) to evaluate blood flow characteristics in orbital vascular tumors.
Five patients were evaluated for vision-threatening orbital vascular tumors. Time-Resolved Imaging of Contrast KineticS (TRICKS) MRA was used to assess blood flow in the tumors.
The images revealed details of the vascular anatomy and flow dynamics. The imaging results were consistent with known properties of orbital vascular lesions, revealing minimal flow in cavernous hemangiomas, low flow in varices and robust flow in a hemangiopericytoma and an arteriovenous malformation. Using this new imaging modality resulted in significant benefit to the patients, including changes in the clinical diagnosis in two of the patients and more precise surgical planning for several of the patients.
Also useful was the ability to utilize dynamic contrast-enhanced MRA sequentially to assess flow in a young patient with an arteriovenous malformation that was being treated via interventional neuroradiology in preparation for surgical vascular debulking. Whereas conventional digital subtraction angiography requires endovascular catheterization and carries significant risk to ocular blood flow, TRICKS MRA was accomplished noninvasively, providing dynamic images of blood flow in the aberrant vascular anatomy and postembolization changes in flow through collateral feeders.
Hatef et al. determined the stage at presentation and the prevalence of systemic involvement in patients with orbital and ocular adnexal lymphoma.
Forty-three patients were included in this study. Nineteen patients had mucosa-associated lymphoid tissue (MALT), nine had follicular lymphoma, nine had diffuse large-cell lymphoma, three had mantle cell lymphoma, two had small lymphocytic lymphoma and one had large T-cell lymphoma.
The staging workup at initial diagnosis of orbital or adnexal lymphoma included chest radiography, orbital CT or MRI, CT of chest, abdomen and pelvis, and bone marrow biopsy in all patients. In addition, 36 patients (84 percent) had total-body positron emission tomography, seven had gallium scans and 16 had gastrointestinal endoscopy. Lymphoma stage at diagnosis was IE in 18 patients (42 percent), II in six patients (14 percent) and IV in 19 patients (44 percent). Six of 19 patients (32 percent) with MALT, seven of nine patients (78 percent) with follicular, six of nine patients (67 percent) with diffuse large-cell and all three patients with mantle cell lymphoma had non-stage-IE disease at presentation. The five-year recurrence-free survival was 64.6 percent for the entire cohort.
The authors conclude that extra-orbital involvement was present at diagnosis in more than half of patients with orbital or ocular adnexal lymphoma and in about one-third of patients with MALT lymphoma, specifically. This finding warrants extensive systemic workup at diagnosis, continued surveillance and consideration of systemic therapy.
Prabhakaran et al. conducted a retrospective study of a large series of patients with orbital and adnexal sarcoidosis.
Only patients with both biopsy-proven noncaseating granuloma involving the orbit or adnexa and evidence of systemic sarcoidosis were included. The study included 26 patients (19 women, seven men; mean age 52 years). Seven patients had been previously diagnosed with sarcoidosis.
The most common presenting feature was a palpable periocular mass followed by discomfort, proptosis, ptosis, dry eye, diplopia and decreased vision. The disease affected the lacrimal gland (42.3 percent), the orbit (38.5 percent), eyelid (11.5 percent) and lacrimal sac (7.7 percent). Among orbital lesions, the anteroinferior quadrant was preferentially involved. Treatment modalities included steroids, surgical debulking and methotrexate. During a mean follow-up of 18.75 months, 84.6 percent of patients showed a complete response to the treatment, but 19.2 percent of patients developed further signs of sarcoidosis.
The authors of the study conclude that orbital involvement with sarcoidosis was more common in women and in those patients over the age of 50. Though a good response to treatment with oral steroids was seen, long-term follow-up was recommended as active systemic disease could develop months to years later.
Leibovitch et al. conducted a pilot study to evaluate the efficacy of intraorbital corticosteroid injection in the management of idiopathic orbital inflammation (IOI).
Ten patients (five men, five women; mean age 49.8) with confirmed IOI and an anteriorly located orbital mass were included in the study. On histology, five cases had chronic nonspecific inflammation, three cases had sclerosing orbital inflammation and two cases had nonspecific granulomatous inflammation. Triamcinolone acetonide (20 to 40 mg) was injected intraorbitally (intralesionally or perilesionally) in all patients. The injection was repeated at four-week intervals if complete resolution was not achieved. Patients were assessed for local and systemic complications of corticosteroid injection. Significant improvement (one case) or complete resolution (eight cases) was noted during a mean follow-up period of 9.8 months.
The authors conclude that intraorbital injection of corticosteroid is an effective treatment modality for idiopathic orbital inflammation, including cases with sclerosing inflammation, and it may be considered as a first line of treatment in selected cases.
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
In an effort to identify sequence variants related to glaucoma risk, Thorleifsson et al. conducted a genomewide association study focusing on patients with glaucoma living in Iceland. The researchers used the Illumina Hap-300 chip and, after quality filtering, tested 304,250 single-nucleotide polymorphisms (SNPs) for association to glaucoma in a sample of 195 cases and 14,474 population controls.
The researchers found SNPs in the 15q24.1 region associated with glaucoma. The association was confined to exfoliation glaucoma (XFG). Two nonsynonymous SNPs in exon 1 of the gene LOXL1 clarified the association, and the data suggested that they conferred risk of XFG mainly through exfoliation syndrome. The investigators pointed out that approximately 25 percent of the general population is homozygous for the highest-risk haplotype, and their risk of suffering from XFG is more than 100 times that of individuals carrying only low-risk haplotypes.
Finally, the product of LOXL1 catalyzed the formation of elastin fibers—a major component of XFG-related lesions. After removing the SNPs in the LOXL1 region, the genome-scan Q-Q plots for primary open-angle glaucoma and glaucoma overall could not be distinguished, thus suggesting that primary open-angle glaucoma may be a more complex disease than XFG.
Douglas Johnson examined 19 autopsy eyes from 14 donors to determine histologic findings after successful argon laser trabeculoplasty in eyes with either primary open-angle or pseudoexfoliative glaucoma. Clinical records allowed the author to determine the effect of the laser in lowering IOP. He also examined 49 eyes with glaucoma that had not undergone the laser procedure and 55 normal eyes as controls.
The author found that laser trabeculoplasty appeared to change the architecture of the juxtacanalicular tissue (JCT) region. Specifically, the JCT expanded into Schlemm’s canal in nontreated areas, often filling it with multiple giant vacuoles and cellular processes. This finding was more common in eyes fixed by posterior chamber perfusion. The author surmised that the change in JCT-region architecture resulted from three factors: a simple stretching, tightening and opening of the trabecular lamellae between laser spots; diversion of aqueous flow to opened meshwork regions with flow being redirected around the impermeable laser spots; and the release of inflammatory factors after laser, which could digest some of the extracellular matrix in the JCT region.
The author warns that these findings could not be extrapolated to selective laser trabeculoplasty.
Campbell et al. set out to discover the extent of institutional academic-industry relationships in medical schools and teaching hospitals across the country. These relationships occur when an academic institution, or any of its senior officials, maintains a financial relationship with or financial interests in a public or private company. The researchers received completed surveys from 459 of 688 eligible department chairs nationwide.
They found that 60 percent of department chairs had a personal relationship with industry, including acting as a consultant (27 percent), a scientific advisory board member (27 percent), a paid speaker (14 percent), an officer (7 percent), a founder (9 percent) or a member of the board of directors (11 percent). Clinical departments were more likely than nonclinical departments to receive research equipment, unrestricted funds, residency or fellowship training support and continuing medical education support.
More than two-thirds of chairs did not feel their relationship with industry had an effect on their professional activities, although they felt that engaging in more than one substantial industry-related activity had a negative impact on a department’s ability to conduct independent, unbiased research.
Studies indicate that the single largest health problem linked to video display terminals (VDTs) is eyestrain. Since meibomian gland dysfunction (MGD) is one of the major causes of ocular discomfort and ocular surface abnormalities, Fenga et al. wondered if this tear film-related condition in any way contributed to the eye discomfort experienced by VDT workers.
For this study, they examined a group of 70 VDT operators who completed a survey and underwent three tests: tear break-up time, fluorescein corneal stain and basal tear secretion.
The researchers found that 52 out of the 70 VDT workers (74.3 percent) had MGD, with a statistically significant higher presence of conjunctival signs and lower tear basal secretion. They also identified a statistically significant correlation between the symptoms of eye discomfort and hours spent in front of a VDT.
Roundup of Other Journals is written by Lori Baker Schena and edited by Deepak P. Edward, MD.