Transactions of the American Ophthalmological Society最新文献

Purpose: To use an integrated proteohistologic approach to gain insight into the anterior segment alterations in the buphthalmic rabbit.

Methods: Eyes from 2- and 5-year-old buphthalmic and normal rabbits (n=20) were studied histologically. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) of aqueous humor (AH) was used to determine differential protein expression between animal groups. Western blot and immunohistochemistry were performed on selected differentially expressed proteins identified by LC-MS/MS.

Results: The buphthalmic rabbits manifested a mild clinical phenotype with typical angle anomalies that appeared progressive by histology. Significantly thickened Descemet's membrane (DM) and anterior lens capsule in all buphthalmic rabbits showed increased fibronectin and collagen-IV immunolabeling. LC-MS/MS applying stringent filtering criteria revealed significant differential expression of several AH proteins in these rabbits. The protein of interest in the 2-year-old group was histidine-rich glycoprotein, and those in the 5-year-old group included alpha-2-HS-glycoprotein, clusterin, apolipoprotein E, interphotoreceptor retinoid-binding protein, transthyretin, cochlin, gelsolin, haptoglobin, hemopexin, and beta-2 microglobulin. The proteomic data for selected proteins was validated by Western blot and immunohistochemistry. A wide range of functional groups were affected by the altered AH proteins. These included extracellular matrix modulation, regulation of apoptosis, oxidative stress, and protein transport.

Conclusions: Multiple anterior segment alterations were histologically identified in the buphthalmic rabbits that showed progressive changes with age. The differentially expressed AH proteins in these rabbits suggest a multifunctional role for AH in modulating pathologic changes in DM, anterior lens capsule, and the angular meshwork in these animals.

Purpose: Overcorrection of hypotropia subsequent to adjustable suture surgery following inferior rectus recession is undesirable, often resulting in persistent diplopia and reoperation. I hypothesized that overcorrection shift after suture adjustment may be unique to thyroid eye disease, and the use of a nonabsorbable suture may reduce the occurrence of overcorrection.

Methods: A retrospective chart review of adult patients who had undergone eye muscle surgery with an adjustable suture technique was performed. Overcorrection shifts that occurred between the time of suture adjustment and 2 months postoperatively were examined. Descriptive statistics, linear regression, Anderson-Darling tests, generalized Pareto distributions, odds ratios, and Fisher tests were performed for two overcorrection shift thresholds (>2 and >5 prism diopters [PD]).

Results: Seventy-seven patients were found: 34 had thyroid eye disease and inferior rectus recession, 30 had no thyroid eye disease and inferior rectus recession, and 13 patients had thyroid eye disease and medial rectus recession. Eighteen cases exceeded the 2 PD threshold, and 12 exceeded the 5 PD threshold. Statistical analyses indicated that overcorrection was associated with thyroid eye disease (P=6.7E-06), inferior rectus surgery (P=6.7E-06), and absorbable sutures (>2 PD: OR=3.7, 95% CI=0.4-35.0, P=0.19; and >5 PD: OR=6.0, 95% CI=1.1-33.5, P=0.041).

Conclusions: After unilateral muscle recession for hypotropia, overcorrection shifts are associated with thyroid eye disease, surgery of the inferior rectus, and use of absorbable sutures. Surgeons performing unilateral inferior rectus recession on adjustable suture in the setting of thyroid eye disease should consider using a nonabsorbable suture to reduce the incidence of postoperative overcorrection.

Purpose: To test the hypothesis that posterior approach ptosis surgery, with or without blepharoplasty, can improve the cosmetic appearance of the eyelid.

Methods: In a retrospective, observational, consecutive case cohort study, 261 patients who had posterior approach upper eyelid ptosis surgery with or without concurrent blepharoplasty performed by one surgeon, between 1997 and 2009, were reviewed. Patients were included if they had symmetric eyelid position within 1.5 mm at 3 months after surgery. Outcome measures were subjective grading of eyelid margin contour, millimeters of tarsal platform show (TPS), and millimeters of eyebrow fat span (BFS). Paired preoperative and postoperative standardized photographs were viewed in masked fashion by three experts.

Results: One hundred and forty patients (55 men, 85 women, mean age 70 years, range 20-93) who underwent 233 posterior approach procedures for correction of upper eyelid ptosis had postoperative eyelid symmetry within 1.5 mm. Concurrent blepharoplasty was performed in 67 cases. Eyelid contour scores were significantly improved following surgery (P=.009). Ptosis surgery, without blepharoplasty, decreased the TPS, from 6.1±2.5 mm to 4.8±2.0 mm (P<.001). Patients who underwent concurrent blepharoplasty had a statistically insignificant increase of TPS from 4.0±3.5 mm to 4.3±3.6 mm, had a decrease of BFS from 20.8±6.3 mm to 17.7±6.4 mm (P=.001), and showed similar BFS symmetry postoperatively, compared to patients who had ptosis surgery only.

Conclusions: posterior approach surgery alone was often successful in controlling TPS: it shortened the TPS. Blepharoplasty combined with posterior approach ptosis surgery tended to lengthen the TPS and shorten the BFS.

Purpose: To design and evaluate a new infant keratometer that incorporates an unobstructed view of the infant with both eyes (open-field design).

Methods: The design of the open-field infant keratometer is presented, and details of its construction are given. The design incorporates a single-ring keratoscope for measurement of corneal astigmatism over a 4-mm region of the cornea and includes a rectangular grid target concentric within the ring to allow for the study of higher-order aberrations of the eye. In order to calibrate the lens and imaging system, a novel telecentric test object was constructed and used. The system was bench calibrated against steel ball bearings of known dimensions and evaluated for accuracy while being used in handheld mode in a group of 16 adult cooperative subjects. It was then evaluated for testability in a group of 10 infants and toddlers.

Results: Results indicate that while the device achieved the goal of creating an open-field instrument containing a single-ring keratoscope with a concentric grid array for the study of higher-order aberrations, additional work is required to establish better control of the vertex distance.

Conclusion: The handheld open-field infant keratometer demonstrates testability suitable for the study of infant corneal astigmatism. Use of collimated light sources in future iterations of the design must be incorporated in order to achieve the accuracy required for clinical investigation.

Purpose: To study vascular endothelial growth factor (VEGF) regulation in the development of intravitreous neovascularization and peripheral avascular retina in peripheral severe retinopathy of prematurity (ROP).

Methods: The rat 50/10 model of ROP mimics zone II, stage 3 severe ROP and recreates fluctuations in transcutaneous oxygen levels in preterm infants. On postnatal (p) day ages p0, p8, p11-p14, and p18, retinas from the model or room-air (RA) age-matched pups were analyzed for mRNA of VEGF splice variants and receptors using real-time polymerase chain reaction or VEGF protein using enzyme-linked immunosorbent assay.

Results: On p14, when retinas were only 70% vascularized in the model but fully vascularized in RA, VEGF₁₆₄ expression was threefold greater in the model compared to RA. On p18, intravitreous neovascularization was associated with a 5-fold increase in VEGF₁₆₄ mRNA in the model compared to RA. By analysis of variance, VEGF₁₆₄ and VEGFR2 mRNAs were up-regulated in association with increasing developmental age (P<.0001 for both comparisons) or exposure to the model compared to RA (P<.0001 and P=.0247, respectively), whereas increasing developmental age was associated only with up-regulated VEGF₁₂₀ (P=.0006), VEGF₁₈₈ (P=.0256), and VEGFR1 (P<.0001) mRNAs. VEGF protein increased significantly in the model and on p14 and p18 compared to RA (P<.0001).

Conclusions: The model mimics contemporary severe ROP in the United States unlike other models of oxygen-induced retinopathy. Compared to RA retinas, VEGF significantly increased in association with avascular retina and intravitreous neovascularization. A hypothesis is proposed that VEGF up-regulation plays a role in the development of both important features.

Purpose: To examine the histopathology of palpebral conjunctiva in patients with thyroid-related orbitopathy. Based on previously published anecdotes, the hypothesis is that conjunctiva shows increased inflammation and fibrosis.

Methods: This was a comparative case series. Superior palpebral conjunctiva was examined from two groups. The study group consisted of 20 patients undergoing thyroid-related upper eyelid retraction surgery. The control group consisted of 18 patients undergoing ptosis repair. Specimens were processed and stained using hematoxylin and eosin and trichrome. Histopathologic grading was performed using light microscopy. Main outcome measures were degree of inflammation and fibrosis, mast cell infiltration, and fibroblast count.

Results: The two groups did not differ with regard to age or gender. Mean degree of inflammation was 1.4 (95% CI: 0.9, 1.9) for the control group and 1.7 (95% CI: 1.3, 2.1) for the study group. Relative intensity of blue from trichrome staining mean was 134.3 (95% CI: 130.3, 138.3) for the control group and 138.6 (95% CI: 133.7, 143.6) for the study group. The Mann-Whitney test showed no difference between groups in inflammation (P=.17), relative blue intensity (P=.11), degree of mast cell infiltration (P=.61), and fibroblast count (P=.45). Point estimates show a trend toward greater inflammation in the study group.

Conclusions: While there is a trend toward higher inflammation in the study group, the superior palpebral conjunctiva of patients with thyroid-related orbitopathy is largely spared from autoimmune changes. This has implications in surgical approaches to eyelid retraction repair.

Purpose: To estimate the short-term variability of macular thickness in eyes with refractory and regressed diabetic macular edema (DME).

Methods: In this retrospective review of consecutive cases from a retina practice, optical coherence tomography (OCT) measurements of macular thickness were extracted from the clinical charts of patients with refractory DME and regressed DME. Variation in macular thickness was defined as maximal central subfield mean thickness (CSMT) minus minimal CSMT during a period of observation in which clinical macular status did not change.

Results: There were 36 eyes of 29 patients in the refractory DME group and 93 eyes of 93 patients in the regressed DME group. Median intervals during which macular status was unchanged and OCTs were collected were 7 months for the refractory DME group and 22 months for the regressed DME group. Baseline CSMTs were 321 μm for the refractory DME group and 217 μm for the regressed DME group. The median variation in CSMT was 89 μm for the refractory DME group and 19 μm for the regressed DME group. Results for total macular volume paralleled those for CSMT.

Conclusions: In consonance with eyes having treatment-naïve DME, eyes with refractory DME have short-term fluctuation in macular thickness larger than OCT measurement variability. In eyes with regressed DME, short-term fluctuation is less than in eyes with refractory DME, yet can also exceed measurement variability. This information is clinically important in deciding whether subsequent treatment is indicated.

Purpose: In a published pilot study, a light-activated microphotodiode-array chip, the artificial silicon retina (ASR), was implanted subretinally in 6 retinitis pigmentosa (RP) patients for up to 18 months. The ASR electrically induced retinal neurotrophic rescue of visual acuity, contrast, and color perception and raised several questions: (1) Would neurotrophic effects develop and persist in additionally implanted RP patients? (2) Could vision in these patients be reliably assessed? (3) Would the ASR be tolerated and function for extended periods?

Methods: Four additional RP patients were implanted and observed along with the 6 pilot patients. Of the 10 patients, 6 had vision levels that allowed for more standardized testing and were followed up for 7+ years utilizing ETDRS charts and a 4-alternative forced choice (AFC) Chow grating acuity test (CGAT). A 10-AFC Chow color test (CCT) extended the range of color vision testing. Histologic examination of the eyes of one patient, who died of an unrelated event, was performed.

Results: The ASR was well tolerated, and improvement and/or slowing of vision loss occurred in all 6 patients. CGAT extended low vision acuity testing by logMAR 0.6. CCT expanded the range of color vision testing and correlated well with PV-16 (r = 0.77). An ASR recovered from a patient 5 years after implantation showed minor disruption and excellent electrical function.

Conclusion: ASR-implanted RP patients experienced prolonged neurotrophic rescue of vision. CGAT and CCT extended the range of acuity and color vision testing in low vision patients. ASR implantation may improve and prolong vision in RP patients.

Purpose: To evaluate the feasibility of developing a novel mini drug pump for ophthalmic use.

Methods: Using principles of microelectromechanical systems engineering, a mini drug pump was fabricated. The pumping mechanism is based on electrolysis, and the pump includes a drug refill port as well as a check valve to control drug delivery. Drug pumps were tested first on the benchtop and then after implantation in rabbits. For the latter, we implanted 4 elliptical (9.9 x 7.7 x 1.8 mm) non-electrically active pumps into 4 rabbits. The procedure is similar to implantation of a glaucoma seton. To determine the ability to refill and also the patency of the cannula, at intervals of 4 to 6 weeks after implantation, we accessed the drug reservoir with a transconjunctival needle and delivered approximately as low as 1 microL of trypan blue solution (0.06%) into the anterior chamber. Animals were followed up by slit-lamp examination, photography, and fluorescein angiography.

Results: Benchtop testing showed 2.0 microL/min delivery when using 0.4 mW of power for electrolysis. One-way valves showed reliable opening pressures of 470 mm Hg. All implanted devices refilled at 4- to 6-week intervals for 4 to 6 months. No infection was seen. No devices extruded. No filtering bleb formed over the implant.

Conclusions: A prototype ocular mini drug pump was built, implanted, and refilled. Such a platform needs more testing to determine the long-term biocompatibility of an electrically controlled implanted pump. Testing with various pharmacologic agents is needed to determine its ultimate potential for ophthalmic use.

Purpose: To test the hypothesis that keratoconus and pellucid patients who have glaucoma or are suspected of having glaucoma have lower corneal hysteresis (CH) and/or corneal resistance factor (CRF) measurements compared to controls.

Methods: A prospective study at a tertiary eye center of keratoconus and pellucid patients with glaucoma or suspected of having glaucoma, and age-matched keratoconus and pellucid controls, was performed. After informed consent was obtained, corneal topography, ocular response analyzer measurements, pachymetry, intraocular pressure, A-scan measurements, Humphrey visual fields (VFs), and disc photos were done. Analyses compared cases to controls on primary (CH and CRF) and secondary variables. Disc photos and VFs were rated in a masked fashion.

Results: The mean CH (8.2, SD=1.6, vs 8.3, SD=1.5) and CRF (7.3, SD=2.0, vs 6.9, SD=2.1) were low and did not differ significantly between 20 study patients (29 eyes) and 40 control patients (61 eyes), respectively. CH had a negative, significant correlation with maximum corneal curvature by topography (P < .002) and positive, significant correlation with central corneal thickness (P < .003). The mean cup-disc ratio was larger among cases than controls (0.54, SD=0.20, vs 0.38, SD=0.20; P = .003). VFs were suggestive of glaucoma more often among the study eyes than controls (11 of 29, 37.9%, vs 8 of 60, 13.3%; P =.019).

Conclusions: CH was low in study and control patients and was correlated with severity of keratoconus/pellucid, but not with glaucoma/suspected glaucoma or control status. Evidence of glaucoma was more common in study eyes than controls, but was present in both.