Transactions of the American Ophthalmological Society最新文献

Purpose: Separation of the neurosensory retina from the retinal pigment epithelium (RPE) yields many morphologic and functional consequences, including death of the photoreceptor cells, Müller cell hypertrophy, and inner retinal rewiring. Many of these changes are due to the separation-induced activation of specific genes. In this work, we define the gene transcription profile within the retina as a function of time after detachment. We also define the early activation of kinases that might be responsible for the detachment-induced changes in gene transcription.

Methods: Separation of the retina from the RPE was induced in Brown-Norway rats by the injection of 1% hyaluronic acid into the subretinal space. Retinas were harvested at 1, 7, and 28 days after separation. Gene transcription profiles for each time point were determined using the Affymetrix Rat 230A gene microarray chip. Transcription levels in detached retinas were compared to those of nondetached retinas with the BRB-ArrayTools Version 3.6.0 using a random variance analysis of variance (ANOVA) model. Confirmation of the significant transcriptional changes for a subset of the genes was performed using microfluidic quantitative real-time polymerase chain reaction (qRT-PCR) assays. Kinase activation was explored using Western blot analysis to look for early phosphorylation of any of the 3 main families of mitogen-activated protein kinases (MAPK): the p38 family, the Janus kinase family, and the p42/p44 family.

Results: Retinas separated from the RPE showed extensive alterations in their gene transcription profile. Many of these changes were initiated as early as 1 day after separation, with significant increases by 7 days. ANOVA analysis defined 144 genes that had significantly altered transcription levels as a function of time after separation when setting a false discovery rate at < or =0.1. Confirmatory RT-PCR was performed on 51 of these 144 genes. Differential transcription detected on the microarray chip was confirmed by qRT-PCR for all 51 genes. Western blot analysis showed that the p42/p44 family of MAPK was phosphorylated within 2 hours of retinal-RPE separation. This phosphorylation was detachment-induced and could be inhibited by specific inhibitors of MAPK phosphorylation.

Conclusions: Separation of the retina from the RPE induces significant alteration in the gene transcription profile within the retina. These profiles are not static, but change as a function of time after detachment. These gene transcription changes are preceded by the activation of the p42/p44 family of MAPK. This altered transcription may serve as the basis for many of the morphologic, biochemical, and functional changes seen within the detached retina.

Purpose: A root cause analysis of the Fusarium keratitis epidemic of 2004-2006 was performed.

Methods: Three US Food and Drug Administration (FDA) documents were analyzed. Poisson and case-control studies were performed on outbreak data from Singapore. Irreversible thermochromic labels were applied to cartons of contact lens solution bottles, which were then subjected to elevated temperatures.

Results: The 1997 FDA guidance document concerning storage temperatures of contact lens care products predicted temperature-related solution instability. Bausch & Lomb (B&L) requested FDA approval for ReNu with MoistureLoc, claiming that it was substantially equivalent to other products. FDA Form 483 stated that cases of ReNu-related Fusarium keratitis from Asia had not been reported, the removal of the product from the Asian markets was unreported, and B&L had not performed biocidal testing on samples associated with Asian cases. The outbreak in Singapore could have been recognized after only 3 cases (Pr = .0067). The cause of the Singapore outbreak could have been determined after the recognition of only 3 (P = .0429), 5 (95% confidence interval [CI], 1.15-126.0), or 15 cases (95% CI, 1.60-14.1). Thermochromic labels can irreversibly change color when exposed to elevated temperatures, thus warning of potential antimicrobial failure.

Conclusions: The worldwide Fusarium keratitis epidemic of 2004-2006 could, theoretically, have been prevented entirely, recognized much earlier, or mitigated by much more rigorous oversight by the FDA, by strict adherence by B&L to FDA guidelines and requirements, by the application of basic statistical methods, and/or by the use of temperature indication technology. The lessons learned from a root cause analysis of this pharmacologic catastrophy may help avert or mitigate future epidemics.

Purpose: To demonstrate that video-rate spectral domain optical coherence tomography (SDOCT) can qualitatively and quantitatively evaluate optic nerve head (ONH) and retinal nerve fiber layer (RNFL) glaucomatous structural changes. To correlate quantitative SDOCT parameters with disc photography and visual fields.

Methods: SDOCT images from 4 glaucoma eyes (4 patients) with varying stages of open-angle glaucoma (ie, early, moderate, late) were qualitatively contrasted with 2 age-matched normal eyes (2 patients). Of 61 other consecutive patients recruited in an institutional setting, 53 eyes (33 patients) met inclusion/exclusion criteria for quantitative studies. Images were obtained using two experimental SDOCT systems, one utilizing a superluminescent diode and the other a titanium:sapphire laser source, with axial resolutions of about 6 microm and 3 microm, respectively.

Results: Classic glaucomatous ONH and RNFL structural changes were seen in SDOCT images. An SDOCT reference plane 139 microm above the retinal pigment epithelium yielded cup-disc ratios that best correlated with masked physician disc photography cup-disc ratio assessments. The minimum distance band, a novel SDOCT neuroretinal rim parameter, showed good correlation with physician cup-disc ratio assessments, visual field mean deviation, and pattern standard deviation (P values range, .0003-.024). RNFL and retinal thickness maps correlated well with disc photography and visual field testing.

Conclusions: To our knowledge, this thesis presents the first comprehensive qualitative and quantitative evaluation of SDOCT images of the ONH and RNFL in glaucoma. This pilot study provides basis for developing more automated quantitative SDOCT-specific glaucoma algorithms needed for future prospective multicenter national trials.

Purpose: To extend upon previous reports, observations, and discussions of intraoperative floppy iris syndrome (IFIS) with the goal of providing new insight into the syndrome's pathophysiology, prevention, and treatment.

Methods: Following a review of IFIS and its relationship to autonomic pharmacology, evidence for anatomic changes following exposure of humans and other animals to autonomic drugs is described. The clinical implications for these findings are discussed as they relate to the treatment and prevention of this syndrome.

Results: IFIS has been associated with the use of adrenergic antagonists even after they have been discontinued years prior to surgery. Some investigators believe that this persistence of IFIS reflects anatomic structural change. Evidence from laboratory experiments and human clinical studies using topically applied and systemic autonomic drugs supports the possibility of anatomic changes coexisting with IFIS observed during cataract surgery.

Conclusions: IFIS is a relatively rare syndrome, often associated with the use of systemic alpha-blockers and conditions that influence dilator muscle tone. Laboratory and clinical evidence supports the possibility of anatomic changes following the use of autonomic drugs. The persistence of IFIS years after cessation of treatment with alpha-blockers suggests that the potential risks of discontinuing these drugs prior to cataract surgery outweigh potential benefits.

Purpose: There is a growing interest in multifocal intraocular lens (IOL) implantation in children because they lose accommodation when a cataract is removed. Many have assumed that very little, if any, eye growth occurs in the second decade of life. Multifocal IOL implantation requires precise biometry to arrive at the correct IOL power for spectacle independence. If the eye grows and the refraction becomes myopic, spectacle dependence may return. Therefore, knowing when the eye has completed its growth is critical to the decision of when to implant a multifocal IOL.

Methods: Ninety-eight eyes were analyzed retrospectively. Each had at least two axial length (AL) measurements using immersion A-scan ultrasound in the second decade of life.

Results: Globe AL was 23.36 +/- 1.52 mm at initial measurement and 23.89 +/- 1.64 mm at last measurement. Measurement data show variable growth throughout the second decade of life. Based on our data, a theoretical patient was constructed with an AL at age 10 of 23.11 mm, who would need an IOL power of 21.5 for emmetropia. That same patient would have an AL of 23.76 mm (IOL power of 19.5) at age 15 and 24.41 mm (IOL power of 17.5) at age 20. That is a 4-diopter change in the IOL power need.

Conclusion: Axial eye growth continues throughout the second decade of life, at least to age 20. These data have important implications for the use of multifocal IOLs in the preteen and teenage years.

Purpose: To report a case series of conjunctival lymphangiectasia treated with liquid nitrogen cryotherapy.

Methods: A 1.5-mm Brymill cryoprobe was applied in a double freeze-thaw method after an incisional biopsy of a portion of the conjunctiva in patients with conjunctival lymphangiectasia. Freeze times were 1 to 2 seconds with thawing of 5 to 10 seconds between treatments. Patients were reexamined at 1 day, 2 weeks, 3 months, 6 months, and yearly following cryotherapy.

Results: Five eyes of 4 patients (3 male and 1 female) with biopsy-proven conjunctival lymphangiectasia underwent liquid nitrogen cryotherapy. The average patient age was 53 years. Ocular examination revealed large lymphatic vessels that were translucent and without conjunctival injection. Subjective symptoms included epiphora, ocular irritation, eye redness, and occasional blurred vision. After treatment with liquid nitrogen cryotherapy, the patients' symptoms and signs resolved within 2 weeks. Lymphangiectasia recurred twice in one patient, at 1 and 3 years postoperatively. In another patient, lymphangiectasia recurred at 6 months. The average time to recurrence in these 3 eyes was 18 months. Average length of follow-up was 24.5 months for all subjects.

Conclusion: Liquid nitrogen cryotherapy may be an effective surgical alternative in the treatment of conjunctival lymphangiectasia. Cryotherapy may need to be repeated in some instances.

Purpose:

The purpose of this study was twofold: first, to prospectively compare visual acuity (VA) scores obtained with Snellen charts versus Early Treatment Diabetic Retinopathy Study (ETDRS) charts in a "real world" retinal practice, and second, to see if there was a difference in visual acuity measurements obtained with ETDRS charts starting at 4 or 2 meters.

Methods: Prospective, consecutive evaluation of patients who underwent best-corrected visual acuity testing of their right eye performed at a single seating by the same experienced, certified vision examiner in the same room with standardized low light conditions using a projected Snellen chart at 20 feet, and two different back-illuminated ETDRS charts placed 4 and 2 meters from the patient.

Results: One hundred sixty-three eyes were included in the study. The mean Snellen VA was 0.67 logMAR (20/94), ETDRS VA at 4 meters was 0.54 logMAR (~20/69), and ETDRS VA at 2 meters was 0.51 logMAR (~20/65). The mean difference was 6.5 letters better on the ETDRS chart (P=.000000001). As the VA worsened, there was increased variability between the charts and the mean discrepancy between charts also increased. Subgroup analysis revealed the greatest difference between charts was in the poor vision subgroup (<20/200) with a difference of 0.2 logMAR (10 letters; P=.0000002). Patients with exudative age-related macular degeneration (AMD) had the greatest disparity on vision testing, but patients with dry AMD and diabetic retinopathy also exhibited significant differences.

Conclusions: Visual acuity scores were significantly better on ETDRS charts compared to Snellen charts. The difference was greatest with poor visual acuity (<20/200) and in patients with exudative AMD. Thus, caution should be exercised when comparing data using the different charts.

Purpose: There have been few reports on the binocular vision results in bilateral pseudophakic children. The author reports on the results of visual and binocular tests personally performed on patients who had the primary insertion of intraocular lenses following the removal of cataracts in their childhood.

Methods: The author visited 4 different medical centers to perform monocular and binocular tests on 21 patients using the same equipment for sensory testing for binocularity on all patients before the history was abstracted from the clinical records. These patients were selected from a consecutive series and followed up for a minimum of 5 years by their ocular surgeons.

Results: The mean patient age at surgery performed on the first eye was 6 years 4 months. The mean age at the date of the author's examination was 16 years 5 months, and the mean length of follow-up was 10 years 4 months. All but 2 patients had motor alignment within 8 prism diopters of orthotropia at near. Fusion and some stereopsis were found to be present in 15 patients, but only 4 of these patients demonstrated fine (60 seconds of arc or better) stereoacuity. Patients with fine vs gross stereoacuity were compared and found to be similar in type of cataract, age at first surgery, interval between surgeries, and length of follow-up and refraction, but to differ in the quality of best-corrected visual acuity.

Conclusion: Although satisfactory motor alignment, fusion, and some stereopsis are present in the majority of patients, fine stereoacuity is uncommon in pseudophakic children.

Introduction: Thyroid orbitopathy is the most common cause of restrictive strabismus. Patients often present with vertical or horizontal double vision, or both, due to restriction involving most commonly the inferior and medial rectus muscles. Traditional muscle surgery involves release of the tight muscles. Previous literature has described a frequent need for secondary operations and an overcorrection incidence of up to 50%. Recognizing that the tight muscles are also limited in their excursion, it was proposed that operating on the better-moving eye, particularly the inferior oblique, might produce an improvement in binocularity and decrease the incidence of overcorrection.

Methods: A total of 37 patients with restrictive strabismus due to thyroid orbitopathy treated at the University of Virginia over 12 years with inferior oblique surgery were retrospectively reviewed.

Results: Eight patients were treated with a combination of inferior oblique surgery and horizontal muscle surgery at the same time. One patient was treated with simultaneous inferior oblique and superior rectus surgery. Seven patients had vertical correction with inferior oblique surgery alone. Twenty-three patients required secondary procedures. Eight patients were overcorrected but only one following primary surgery. At the time of last follow-up, ranging from 6 months to 8 years, 33 patients had no diplopia, 2 had minimal diplopia, and 2 had persistent diplopia. All but two were completely functional.

Conclusion: Inferior oblique surgery by balancing the overall excursion of extraocular muscles in thyroid patients may produce binocularity in primary position and down reading gaze. The amount of vertical correction from inferior oblique surgery alone is limited, often requiring ipsilateral superior or contralateral inferior rectus surgery. Inferior oblique surgery likely increases the area of binocular single vision and decreases the incidence of overcorrection. The use of Hess screen and binocular single vision fields is helpful in assessment and planning of surgery in these patients.

Purpose: To understand ophthalmologists' current perceptions and treatment of patients with moderate to severe dry eye syndrome (DED).

Methods: An online survey was distributed to 7,882 ophthalmologists, including 51 corneal specialists, throughout the United States from October 9 to 21, 2008. The response rate was 3.1% (n = 245), typical for this type of survey. Those who treated 4 or more patients with moderate to severe DED per month (235 of 245 [96%]) were asked to complete the survey.

Results: Ninety-four percent of respondents agreed that more treatment options are needed for moderate to severe DED. Corneal specialists were more likely to strongly agree (63%) than general ophthalmologists (54%). Only 33% overall felt that current therapies were extremely or very effective for moderate DED, and only 5% for severe disease. Ninety-two percent agreed that multiple therapeutic agents are needed to manage moderate to severe DED. The respondents reported prescribing, recommending, or suggesting a mean of 3.2 different treatment approaches over the course of a year for patients with moderate DED and 4.9 for patients with severe DED. The most highly ranked goals in treatment of moderate to severe DED were maintaining and protecting the ocular surface (ranked 1 or 2 by 74%) and lubricating and hydrating the ocular surface (ranked 1 or 2 by 67%). Corneal specialists ranked maintaining and protecting the ocular surface even higher (ranked 1 or 2 by 82%).

Conclusions: Results reflected the difficulty of treating more serious moderate to severe cases, the importance of using multiple treatment approaches, the limitations of current treatment options, and the need for additional treatment options.