Latanoprost-associated cystoid macular edema in a patient with phakic eyes.

Here, we report a case of bilateral cystoid macular edema (CME) in a woman with phakic eyes after 22 years of latanoprost use. Optical coherence tomography revealed multiple intraretinal cysts, and fluorescein angiography revealed characteristic petaloid dye leakage from the perifoveal capillaries. A cause-effect relationship was suspected when CME resolved after switching from latanoprost to dorzolamide, as confirmed by positive rechallenge and dechallenge tests. Since prostaglandin analog-induced CME has only been reported in patients with pseudophakic, aphakic, or phakic eyes with retinal conditions predisposing to macular edema, this seems to be the first reported case of latanoprost-induced CME in a patient with phakic eyes without retinal risk factors.

Different Disc Characteristics Associated With High Myopia and the Location of Glaucomatous Damage in Primary Open-Angle Glaucoma and Normal-Tension Glaucoma.

PRéCIS:: Disc tilt is a characteristic of high myopia and related to lower wedge-shaped retinal nerve fiber layer (RNFL) defects in normal-tension glaucoma (NTG). In primary open-angle glaucoma (POAG), the direction of disc torsion corresponds to the location of wedge-shaped RNFL defects. PURPOSE: To evaluate the disc characteristics in high myopia and the relationships between disc tilt and torsion and the location of wedge-shaped RNFL defects in primary POAG and NTG. MATERIALS AND METHODS: The differences in disc properties and clinical characteristics between POAG (n=53) and NTG (n=82), and between high myopic (<-6 D, n=77) and non-high myopic (≥-6 D, n=58) glaucoma, were investigated. The association between disc tilt and torsion and the location of wedge-shaped RNFL defects in POAG and NTG were assessed by univariate and multivariate logistic regression analyses. RESULTS: In NTG, but not in POAG, high myopia eyes had significantly smaller discs, a lower tilt ratio (0.73±0.09), and more disc tilt (56.5%) than did non-high myopia eyes (0.80±0.09, 33.3%). In POAG, eyes with lower wedge-shaped RNFL defects had a significantly smaller torsion angle (-5.44±19.62 degrees, inferior disc torsion) than did eyes with upper defects (9.70±23.62 degrees, superior disc torsion; P=0.014). In NTG, a significantly decreased tilt ratio (0.74±0.93; P=0.001) and more disc tilt (55.9%, P=0.005) were found in eyes with lower wedge-shaped RNFL defects than in eyes with upper defects (0.81±0.09; 21.7%). The torsion degree and tilt ratio were the only factors associated with the location of wedge-shaped RNFL defects in POAG and NTG, respectively. CONCLUSIONS: In NTG, smaller and tilted discs were the characteristics of high myopia. Disc tilt was associated with lower wedge-shaped RNFL defects. In POAG, the direction of disc torsion corresponded to the location of the wedge-shaped RNFL defects.

Bilateral acute angle closure glaucoma and myopic shift by topiramate-induced ciliochoroidal effusion: case report and literature review.

PURPOSE: To report two cases of ciliochoroidal effusion after the usage of topiramate. CASES: Two middle-aged women experienced sudden onset of acute glaucoma and acquired myopia after taking topiramate. Ultrasound biomicroscopy demonstrated bilateral ciliochoroidal effusion and angle closure. The A-scan ultrasonography revealed shallow anterior chamber and thick lens. After the treatment and drug withdrawal, intraocular pressure, refractive status and angle anatomy returned to normal and there was resolution of ciliochoroidal effusion. During the clinical course, the anterior chamber depth (ACD) increased from 2.02 to 3.30 mm (1.28 mm of changes) OD and from 1.94 to 3.36 mm (1.42 mm of changes) OS. The lens thickness (LT) became thinner from 4.53 to 4.31 mm (0.22 mm of changes) OD and from 4.59 to 4.30 mm (0.29 mm of changes) OS in the first case. In the second case, the ACD increased from 2.33 to 3.07 mm (0.74 mm of changes) OD and from 2.30 to 3.05 mm (0.75 mm of changes) OS. The LT became thinner from 4.42 to 4.27 mm (0.15 mm of changes) OD and from 4.38 to 4.26 mm (0.12 mm of changes) OS. The forward displacement of the lens-iris diaphragm contributed more to the shallowness of the anterior chamber than the thickening of the lens itself (only accounting for 20%). CONCLUSION: Topiramate-induced bilateral acute angle closure glaucoma and myopic shift was due to ciliochoroidal effusion which resulted in thicker lens and shallow anterior chamber. The later was mainly due to anterior displacement of the lens-iris diaphragm.

Pigment Epithelial-Derived Factor Peptide Regenerated Limbus Serves as Regeneration Source for Limbal Regeneration in Rabbit Limbal Deficiency.

PURPOSE: To demonstrate that a 44-amino acid peptide from pigment epithelial-derived factor (PEDF) induces the regeneration of limbal excision wound, and the regenerated limbus can act as the regeneration source for new limbal excisional injuries in rabbit model of limbal deficiency. METHODS: Half circumference partial limbal excision was followed by PEDF peptide treatment to achieve limbal wound regeneration. Three months later, a second stage half circumference partial limbal excision removed the remaining native limbal tissue followed by PEDF peptide treatment. The structure and function of the regenerated limbus were analyzed at 3 and 6 months. Conjunctivalization was analyzed by impression cytology. Immunohistochemical analysis was performed with antibodies to corneal epithelium-associated keratin 3 (K3), conjunctival epithelium-associated keratin 13 (K13), ΔNp63α, ABCG2, and BrdU. Extensive limbal excision was performed to examine the regeneration potential of the PEDF peptide. RESULTS: Total limbal stem cell deficiency occurred with severe inflammation and conjunctivalization of the limbal wound and adjacent cornea in vehicle control eyes. In PEDF peptide treated eyes, the regenerated limbus prevented fibrovascular invasion and goblet cell migration into the corneal surface. Immunohistochemical staining of the regenerated limbus showed a wide distribution of cells expressing ΔNp63α and ABCG2 as in the native limbus. BrdU labeling assay revealed the presence of slow-cycling cells in the basal layer of the regenerated limbus. The PEDF peptide can heal extensive limbal excisional wounds and sustain ocular surface integrity. CONCLUSIONS: The addition of PEDF peptide has the potential to repair limbal excisional wounds with the recovery of normal limbus-like anatomy and function. The PEDF peptide is a potential remedy for extensive limbal injury.

The Optic Nerve Head in Primary Open-Angle Glaucoma Eyes With High Myopia: Characteristics and Association With Visual Field Defects.

PURPOSE: To evaluate the morphologic characteristics of optic neuropathy and its association with visual field (VF) defects in primary open-angle glaucoma (POAG) eyes with high myopia. METHODS: In this cross-sectional study, we reviewed data from 375 Taiwanese patients (375 eyes) of POAG, ages 20 to 60 years. Optic disc photographs were used for planimetric measurements of morphologic variables. The myopic refraction was divided into high myopia (<-6.0 D) and nonhigh myopia (moderate myopia to hyperopia). The optic disc area was classified as moderate (1.59 to 2.85 mm(2)), large, and small. Differences in characteristics between groups, correlations with the disc area, and factors associated with VF defects were determined. RESULTS: Of the 142 highly myopic eyes, 33 (23%) had a large disc, 26 (18%) had a small disc, and 55 (39%) had a tilted disc. Large discs had a higher cup-to-disc (C/D) area ratio and a higher tilt ratio; small discs had a smaller rim area and a lower tilt ratio (all P<0.05). Characteristics associated with high myopia included a smaller rim area, a higher C/D area ratio, and a lower tilt ratio (all P<0.001). In logistic regression, the refraction, the C/D area ratio, the rim area, and the tilt ratio (all P<0.05) were associated with VF defects. CONCLUSIONS: In Taiwanese individuals with POAG, our study found that tilted, large, or small discs were prevalent in highly myopic eyes. Of these characteristics, only the disc tilt and high myopia by itself were associated with the severity of glaucomatous optic neuropathy.

PEDF-derived peptide promotes skeletal muscle regeneration through its mitogenic effect on muscle progenitor cells.

In response injury, intrinsic repair mechanisms are activated in skeletal muscle to replace the damaged muscle fibers with new muscle fibers. The regeneration process starts with the proliferation of satellite cells to give rise to myoblasts, which subsequently differentiate terminally into myofibers. Here, we investigated the promotion effect of pigment epithelial-derived factor (PEDF) on muscle regeneration. We report that PEDF and a synthetic PEDF-derived short peptide (PSP; residues Ser(93)-Leu(112)) induce satellite cell proliferation in vitro and promote muscle regeneration in vivo. Extensively, soleus muscle necrosis was induced in rats by bupivacaine, and an injectable alginate gel was used to release the PSP in the injured muscle. PSP delivery was found to stimulate satellite cell proliferation in damaged muscle and enhance the growth of regenerating myofibers, with complete regeneration of normal muscle mass by 2 wk. In cell culture, PEDF/PSP stimulated C2C12 myoblast proliferation, together with a rise in cyclin D1 expression. PEDF induced the phosphorylation of ERK1/2, Akt, and STAT3 in C2C12 myoblasts. Blocking the activity of ERK, Akt, or STAT3 with pharmacological inhibitors attenuated the effects of PEDF/PSP on the induction of C2C12 cell proliferation and cyclin D1 expression. Moreover, 5-bromo-2'-deoxyuridine pulse-labeling demonstrated that PEDF/PSP stimulated primary rat satellite cell proliferation in myofibers in vitro. In summary, we report for the first time that PSP is capable of promoting the regeneration of skeletal muscle. The signaling mechanism involves the ERK, AKT, and STAT3 pathways. These results show the potential utility of this PEDF peptide for muscle regeneration.

Pigment Epithelial-Derived Factor Peptide Facilitates the Regeneration of a Functional Limbus in Rabbit Partial Limbal Deficiency.

PURPOSE: To investigate the potential of a pigment epithelial-derived factor (PEDF) peptide 44-mer to promote limbal regeneration in a rabbit partial limbal deficiency model. METHODS: Limbal excision (180°) was created surgically, and topical application of 44-mer-containing ointment once a day for 2 weeks was started immediately after injury. Limbal barrier function was inspected at 2 and 6 months after treatment. Corneal neovascularization was observed under slit-lamp microscope. The presence of goblet cells on the corneal surface was examined using impression cytology. The resulting repair tissue was assessed by immunohistochemical staining with antibodies for putative limbal stem cell (LSC) markers ΔNp63α and ABCG2. Cells harvested from the regenerated tissue were analyzed for colony-forming capacity and expression of LSC markers by immunostaining assay and quantitative real-time PCR (qPCR). RESULTS: Eyes treated with the 44-mer blocked vascularization and goblet cell migration onto the corneal surface. By means of immunohistochemical staining and cell isolation in the repair tissue, we showed that LSCs were widely distributed at the regenerated tissue after 44-mer treatment. The repaired limbus contributed robustly to corneal wound healing as effectively as undamaged limbus. CONCLUSIONS: We demonstrated that 44-mer regenerates a functional limbus-like structure on limbal excision wounds. Our finding suggests that the PEDF peptide derivative may be an innovative strategy for tissue engineering and repair therapy in partial LSC deficiency diseases.

Characteristics of peripapillary choroidal cavitation detected by optical coherence tomography.

PURPOSE: To evaluate the clinical features of peripapillary choroidal cavitation (PCC) detected by optical coherence tomography (OCT). DESIGN: Retrospective, observational case series. PARTICIPANTS: One hundred twenty-two eyes from 83 patients diagnosed with PCC by OCT database review were included in this study. METHODS: Stereoscopic color fundus photographs from eyes with PCC were reviewed by 2 independent ophthalmologists. They were masked to the refractive error, axial length, and OCT findings. MAIN OUTCOME MEASURES: Chart review and data analysis included gender, age, best-corrected visual acuity (BCVA), refractive error, axial length, clinical appearance of the peripapillary area, and associated funduscopic abnormalities. RESULTS: One hundred twenty-two eyes with PCC from 83 patients were analyzed. Among the patients, 41.8% were men and 58.2% were women. The mean age was 48.2 ± 12.6 years and mean BCVA in logarithm of the minimum angle of resolution units was 0.23 ± 0.43. The mean refractive error in spherical equivalent was -9.03 ± 5.11 diopters (D) and mean axial length (AL) was 27.36 ± 2.09 mm. With respect to refractive error, 90 eyes (73.8%) were highly myopic (≥-6.00 D), 24 eyes (19.7%) had low myopia (<-6.00 D), 5 eyes (4.1%) were emmetropic (1.00 to -1.00 D), and 3 eyes (2.6%) were hyperopic (>1.00 D). Forty eyes (32.8%) with PCC had AL of less than 26.50 mm (mean, 25.11 ± 1.07 mm; range, 22.51-26.42 mm). Patients with eyes with PCC that had low myopia, were emmetropic, and were hyperopic also were significantly older than patients with highly myopic eyes (P<0.05). Stereoscopic fundus photographs demonstrated a yellow-orange, localized, well-circumscribed peripapillary lesion in 57 (46.7%) eyes with PCC. A PCC with opening was observed in 14 (26.4%) of 53 eyes with excavated myopic conus and in 5 (7.2%) of 69 eyes without excavated myopic conus (P<0.05). CONCLUSIONS: This study demonstrated that peripapillary choroidal cavitation is common and not exclusive to highly myopic eyes. The funduscopic finding of a yellow-orange peripapillary abnormality may not be evident in all eyes with demonstrable PCC by OCT. Although its pathogenesis and pathologic significance require further investigation, PCC may be a degenerative change in aging eyes.

Comparison of matrix perimetry with octopus perimetry for assessing glaucomatous visual field defects.

PURPOSE: To compare Humphrey Matrix (Matrix) with Octopus perimetry for assessing visual field (VF) indices, size, severity, and location in the glaucomatous VF defect. METHODS: Matrix (30-2 threshold program) and Octopus 1-2-3 perimetry (G1X program) were conducted on 60 eyes of 60 patients with primary open-angle glaucoma. The VF indices derived by Matrix (mean deviation, pattern standard deviation), and Octopus (mean defect, square root of loss variance, corrected loss variance) were compared, as were the size (percentage of points depressed < 5% or < 1%) and the severity (score and Hodapp-Parrish-Anderson grade) of the VF defect. RESULTS: Matrix and Octopus results agreed well overall for VF indices, size, severity, and locations of the VF defect. The mean deviation and pattern standard deviation in Matrix were significantly higher than the mean defect, square root of loss variance and square root of corrected loss variance in Octopus. On the total deviation plot, the size of the VF defect in the superior and nasal fields reported by Matrix was significantly higher than by Octopus. The VF defect score by Matrix was significantly higher than that by Octopus in the superior, nasal, and whole fields. More eyes had a worse grade by Matrix than by Octopus. CONCLUSIONS: Matrix compared well with Octopus in detecting glaucomatous visual field defects. However, the defects reported by Matrix were larger and more severe than with Octopus.

Clinical characteristics and prognostic significance of disc hemorrhage in open-angle and angle-closure glaucoma.

PURPOSE: To analyze the clinical characteristics and prognostic significance of disc hemorrhage in primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), and primary angle-closure glaucoma (PACG). METHODS: Records of patients with POAG, NTG, or PACG and a history of disc hemorrhage were collected for this retrospective, observational cohort study. RESULTS: Of 1134 patients with POAG, 513 with NTG and 770 with PACG, 63 (5.6%), 36 (7.0%), and 44 (5.7%), respectively, had disc hemorrhage over a mean of 9 years of follow-up. There were no significant differences in the laterality, episodes, duration of hemorrhage, and frequency of recurrent hemorrhage among the 3 types. The intraocular pressure and cup-to-disc ratio did not differ significantly between eyes with and fellow eyes without hemorrhage. There was a significant association between disc hemorrhage and visual field progression [odds ratio: 2.78 (P = 0.004), 3.75 (P = 0.040), and 4.50 (P = 0.011) for POAG, NTG, and PACG, respectively]. CONCLUSIONS: Normal tension glaucoma has the highest incidence of disc hemorrhage, followed by PACG and POAG, which have similar incidence. The clinical characteristics of hemorrhage are not different among 3 types of glaucoma. The presence of disc hemorrhage is associated with the progression of glaucomatous optic neuropathy and visual field defects in POAG, NTG, and PACG.

Progression of optic neuropathy after disc hemorrhage in primary angle-closure glaucoma.

BACKGROUND: We describe progressive optic neuropathy after recurrent disc hemorrhages in patients with primary angle-closure glaucoma. CASES: Three Taiwanese Chinese patients with primary angle-closure glaucoma and recurrent disc hemorrhages were followed for 10 years. OBSERVATIONS: Despite good control of intraocular pressure, progressive enlargement of optic disc cupping and visual field defects corresponding to the location of disc hemorrhages were noted after recurrent hemorrhages. CONCLUSIONS: Disc hemorrhages are not particularly rare in primary angle-closure glaucoma and may be a sign of a poor prognosis.

Characteristics of disc hemorrhage in primary angle-closure glaucoma.

PURPOSE: To analyze the characteristics of disc hemorrhage in primary angle-closure glaucoma (PACG). DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Patients seen in glaucoma clinics with PACG and a history of disc hemorrhage. METHODS: Goldmann tonometry, gonioscopy, ophthalmoscopy, and automated perimetry. MAIN OUTCOME MEASURES: Location, number of episodes, and duration of disc hemorrhage; comparison of intraocular pressure (IOP) and cup-to-disc ratio (CDR) in eyes with and fellow eyes without hemorrhage; and changes of CDR and visual fields (VFs) on follow-up. RESULTS: The mean duration of follow-up was 109.2+/-63 months (range, 7-261). Of 770 patients with PACG, 44 (5.7%) had disc hemorrhage at some point in their history, of whom 30 (68%) had unilateral and 14 (32%) had bilateral hemorrhages, either alternately or simultaneously in both eyes. There were a total of 111 hemorrhages in 58 eyes, including 23 eyes (40%) with recurrent hemorrhages. Of the 111 total hemorrhages, 85 (77%) occurred in the inferotemporal and 19 (17%) in the superotemporal sector of the disc. Among 23 eyes with recurrent disc hemorrhages, 11 (48%) had recurrence in the same sector of the disc. The average duration of hemorrhages was 12.8+/-8.1 weeks. The IOP and CDR did not differ significantly between eyes with and fellow eyes without hemorrhage. For patients with unilateral disc hemorrhage, progressive changes in the CDR were found in both the eyes with and fellow eyes without disc hemorrhage, but VF defects worsened only in eyes with disc hemorrhage. CONCLUSIONS: The incidence of disc hemorrhage in patients with PACG was 5.7% over 9 years of follow-up. Despite its relative infrequency, disc hemorrhage in PACG was associated with progression of glaucomatous optic neuropathy and VF defects.

Ocular biometry in acute and chronic angle-closure glaucoma.

AIM: To evaluate the biometric difference between eyes with acute angle-closure (AAC) attack, their uninvolved fellow eyes and eyes with chronic angle-closure glaucoma (CACG). METHODS: Patients with prior laser iridotomy on both eyes for unilateral AAC attack or CACG were recruited. We compared ocular biometric parameters by A-scan ultrasonography of the acutely affected eyes with those of the uninvolved fellow eyes and with eyes affected by CACG. RESULTS: Thirty-three patients with unilateral AAC attack and 41 patients with CACG were included. The eyes with AAC attack had a significantly shallower anterior chamber depth (ACD), thicker lens, shorter axial length, higher lens/axial length factor and more anteriorly positioned lens than the eyes with CACG. The uninvolved fellow eyes had a significantly shallower ACD, shorter axial length and higher lens/axial length factor compared with the eyes with CACG. Acutely affected eyes had a shallower ACD and more anteriorly positioned lens than did the uninvolved fellow eyes. CONCLUSION: Eyes with AAC attack had a more crowded anterior segment compared with uninvolved fellow eyes and those affected by CACG. In addition to ACD, relative lens size, represented by the lens/axial length factor, and relative lens position appear to play important roles in the development of AAC attack.

2-Deoxy-D-glucose protects retinal ganglion cells against excitotoxicity.

Caloric restriction mimicked by administration of 2-deoxy-D-glucose (2DG) has been shown to protect cerebral neurons against ischemia and excitotoxicity. This study examined the protective effects of pretreatment with 2DG on retinal neurons in N-methyl-D-aspartate (NMDA) excitotoxicity in rats. There was a significantly reduced number of TUNEL-labeled cells in the retinal ganglion cell layer 18 h after intravitreal injection of NMDA with 2DG pretreatment. At 7 days after NMDA, 2DG pretreatment significantly preserved neurons in the retinal ganglion cell layer and reduced immunoreactivity of glial fibrillary acidic proteins in retinas. Our findings demonstrate that caloric restriction mimicked by 2DG protects retinas from NMDA excitotoxicity.