Ischemic tissue injury and progenitor cell tropism: significant contributors to the pathogenesis of pterygium.

Pterygium is a common ocular surface disease characterized by triangular wing-like growth consisting of subconjunctival hypertrophic connective tissue. Pterygium is easily complicated by adhesion to the eyelid and diplopia related to motility restriction of the eyeball. Beyond the cosmetic problems, this condition has a catastrophic effect on quality of life. Post-surgical recurrence rates of pterygium excision have been reported to be very high. Therefore, identifying the distinct pathogenic pathways of the disease may lead to new therapeutic strategies with lower risk of treatment failure. Based on the relatively low vascularity and known-predominance of disease occurrence in the nasal conjunctiva of normal eyes, we proposed that hypoxic ischemic injury can elicit the development of pterygium. Here, we review hypoxia-inducible factor (HIF)-1alpha-induced activation of the stromal cell-derived factor-1 (SDF-1)/chemokine receptor type 4 (CXCR4) signaling pathway as a possible mechanism. Supporting this concept of pathogenic mechanism, we also highlight bone marrow-derived progenitor cell tropism as a main contributor to pterygium pathogenesis.

Vitrectomy combined with intravitreal triamcinolone acetonide injection and macular laser photocoagulation for nontractional diabetic macular edema.

PURPOSE: To evaluate the efficacy of vitrectomy combined with intravitreal injection of triamcinolone acetonide (IVTA) and macular laser photocoagulation for the treatment of nontractional diabetic macular edema (DME) refractory to anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Twenty-eight eyes from 28 subjects who were diagnosed with nontractional DME refractory to three or more sequential anti-VEGF injections underwent sequential vitrectomy, IVTA, and macular laser photocoagulation. Changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST) during the six months following vitrectomy were evaluated. Additionally, the CST and BCVA outcomes were compared with those of 26 eyes treated with the same triple therapy for nontractional DME refractory to conventional treatment, such as IVTA or macular laser photocoagulation, or both. RESULTS: The mean logarithm of the minimum angle of resolution BCVAs before and one, three, and six months after vitrectomy were 0.44 ± 0.15, 0.36 ± 0.18, 0.31 ± 0.14, and 0.34 ± 0.22, respectively. The mean CSTs were 433.3 ± 77.9, 329.9 ± 59.4, 307.2 ± 60.2, and 310.1 ± 80.1 microns, respectively. The values of both BCVA and CST at one, three, and six months were significantly improved from baseline (p < 0.05). The extent of CST reduction during the first month after triple therapy was greater in eyes refractory to conventional treatment than in eyes refractory to anti-VEGF (p = 0.012). CONCLUSIONS: Vitrectomy combined with IVTA and macular laser photocoagulation had a beneficial effect on both anatomical and functional outcomes in eyes with nontractional DME refractory to anti-VEGF therapy.

Healing of conjunctival wounds after 23-gauge sutureless vitrectomy.

PURPOSE: To evaluate the healing course of conjunctival wounds in eyes undergoing 23-gauge sutureless vitrectomy and to determine when the potential for ocular surface fluid contamination is no longer a serious concern. METHODS: Prospective observational case series. Thirty-four eyes from 34 patients that underwent transconjunctival 23-gauge sutureless vitrectomies were included. A total of 102 conjunctival wounds overlaying the sutureless sclerotomies from 34 eyes were evaluated prospectively by slit-lamp biomicroscopic examination using cobalt blue light with fluorescein dye staining. The configuration and size of the conjunctival wounds were measured with fluorescein dye staining postoperatively on Days 1, 4, 8, and 15. RESULTS: Seventy-five conjunctival wounds (73.5%) had not healed completely 4 days after the operation. Eight days after surgery, the proportion of eyes with fluorescein staining at the conjunctival wound decreased to 13.7%. Fifteen days after surgery, there was no fluorescein staining at the conjunctival wound in any case. Combined cataract extraction was a factor that delayed the healing of the conjunctival wound (P = 0.036). CONCLUSION: The results suggest that, regarding conjunctival integrity, patients should be safe from intraocular contamination 15 days after 23-gauge sutureless vitrectomy. Concomitant cataract extraction might lengthen the conjunctival wound healing process in these eyes.

Thinner choroid and greater drusen extent in retinal angiomatous proliferation than in typical exudative age-related macular degeneration.

PURPOSE: To compare choroidal thickness and extent and density of drusen between eyes with typical exudative age-related macular degeneration (AMD) and eyes with retinal angiomatous proliferation (RAP). DESIGN: Observational case series. METHODS: Twenty-four eyes with typical exudative AMD and 20 eyes with RAP were included. Subfoveal choroidal thickness was measured using enhanced depth imaging optical coherence tomography. Eyes were classified into 3 groups according to the extent of drusen distribution in the fundus photograph. Density of drusen was estimated based on optical coherence tomography images of the fellow eye. The proportion of the length beneath the drusen per the entire length of the Bruch membrane was defined as the density of drusen. Subfoveal choroidal thickness, extent of drusen distribution, and the density of drusen were compared between typical exudative AMD and RAP. RESULTS: Mean ± standard deviation subfoveal choroidal thickness in eyes with typical exudative AMD and eyes with RAP was 184.9 ± 68.5 µm and 139.0 ± 65.5 µm, respectively (P = .035). The mean density of drusen was 0.06 ± 0.08 and 0.24 ± 0.12, respectively (P < .001). In the typical exudative AMD group, 19, 3, and 2 eyes were included in the small extent group (two thirds), respectively. In the RAP group, 3, 14, and 3 eyes were included in each aforementioned group, respectively (P = .001). CONCLUSIONS: The thinner subfoveal choroidal thickness and greater extent and density of drusen in RAP than the typical exudative AMD may suggest compromised choroidal perfusion in the development of RAP.

Assessment of retinal layers and visual rehabilitation after epiretinal membrane removal.

BACKGROUND: To evaluate the changes in visual acuity, metamorphopsia, and thickness of retinal layers after epiretinal membrane (ERM) removal and to investigate factors associated with visual function. METHODS: This prospective study included 52 eyes of 52 patients who underwent surgery for idiopathic ERM. Changes in visual acuity, metamorphopsia score (M-score) using M-chart, and parafoveal thickness of each retinal layer were evaluated preoperatively and at 2-month and 6-month postoperative follow-up visits. Factors associated with visual acuity and M-score were investigated. RESULTS: Although continuous improvement in visual acuity and decrease in the thickness of parafoveal retinal layers following ERM removal was observed, relatively slow improvement in M-score was noted with values of 0.32 ± 0.27, 0.44 ± 0.46, and 0.23 ± 0.23, respectively at the defined time points. A preoperative increase in the thickness of parafoveal retina was mainly caused by increased thickness of inner retinal layers. Preoperative thickness of inner nuclear layer (INL) were closely associated with preoperative, postoperative visual acuity, and preoperative M-score (p = 0.001, 0.012, and 0.027, respectively). CONCLUSIONS: Compared with the postoperative improvement in visual acuity, the postoperative improvement in metamorphopsia was a rather slow process. Parafoveal INL thickness was found to be a significant structural factor for visual acuity and metamorphopsia in ERM.

Overestimation of subfoveal choroidal thickness by measurement based on horizontally compressed optical coherence tomography images.

PURPOSE: To measure the difference in subfoveal choroidal thickness between 1:1 pixel (horizontally compressed) images and 1:1 micron images in age-related macular degeneration. METHODS: This study included 122 eyes from 122 patients diagnosed with age-related macular degeneration. Choroidal thickness was measured using enhanced-depth imaging optical coherence tomography. The measurement line was drawn as a perpendicular line between Bruch's membrane and the chorio-scleral interface. The thickness was compared between measurements based on a 1:1 pixel image and a 1:1 micron image. Eyes with a straight vertical measurement line and oblique measurement line were classified into vertical measurement group and oblique measurement group, respectively. Intra-group comparisons of subfoveal choroidal thickness measurements based on the 1:1 pixel images and the 1:1 micron images were performed for the two groups. RESULTS: The mean subfoveal choroidal thicknesses measured on the 1:1 pixel images and the 1:1 micron images were 232.3 ± 106.4 µm and 228.9 ± 108.1 µm, respectively (p = 0.003). In the vertical measurement group (86 eyes), the mean subfoveal choroidal thickness was 226.3 ± 109.9 µm and 225.4 ± 112.0 µm, respectively (p = 0.423). In the oblique measurement group (36 eyes), the thickness was 246.5 ± 97.3 µm and 237.5 ± 98.9 µm, respectively (p < 0.001). CONCLUSIONS: Significant overestimation of the subfoveal choroidal thickness was noted when it was measured on a 1:1 pixel image. This finding suggests that the measurement of choroidal thickness should be performed based on a 1:1 micron image, especially if the measurement line is not vertical.

Topographic changes of retinal layers after resolution of acute retinal detachment.

PURPOSE: To investigate changes in thickness profiles of retinal layers after resolution of recent onset rhegmatogenous retinal detachment METHODS: Spectral domain optical coherence tomography (SD-OCT) scans were performed for 28 patients diagnosed with unilateral inferior half or superior half retinal detachment who underwent retinal reattachment surgery. The thickness of each retinal layer was measured at 3000 µm and 2800 µm in the superior and inferior directions from the foveal center. The thicknesses of each retinal layer of the reattached retina were compared with those of the undetached region of the retina of the same eye. RESULTS: Sixteen patients were diagnosed with superior half and 12 patients were diagnosed with inferior half retinal detachment. The mean duration of retinal detachment was 6.9 ± 3.9 days. SD-OCT scans were performed 10.4 ± 6.9 months after the surgery. The thicknesses of the outer nuclear layer and photoreceptor layer in the reattached retina were significantly thinner than those of the undetached retina (P = 0.012, and P = 0.018, respectively). CONCLUSIONS: Our findings suggest that prominent retinal structural sequelae, especially in outer nuclear layer and photoreceptor layer, can be induced by a short duration of retinal detachment. Our findings also underscore the important role of initial retinal injuries that occur within the first several days on the long term structural prognosis. (ClinicalTrials.gov number, NCT01587794).

Asymmetric elongation of foveal tissue after macular hole surgery and its impact on metamorphopsia.

PURPOSE: To evaluate the elongation profile of foveal tissue after macular hole (MH) surgery and to investigate its impact on visual function. DESIGN: Prospective, interventional case series. PARTICIPANTS: Thirty-one eyes from 31 patients who underwent surgery for an MH less than 400 µm in diameter. METHODS: The distance between the parafoveal edge of the outer plexiform layer (OPL) was defined as the inter-OPL distance and measured on the basis of optical coherence tomography images at the first postoperative visit and the 2- and 6-month postoperative visits. Further elongation of the foveal tissue in certain directions was defined as asymmetric elongation. The association of the mean degree of asymmetric elongation with visual acuity and metamorphopsia score (M-score) outcome was evaluated. MAIN OUTCOME MEASURES: Inter-OPL distance and M-score. RESULTS: Macular hole sealing was noted in all eyes after surgery. The horizontal inter-OPL distances measured at the defined time points were 361.6±99.6 µm, 558.8±93.3 µm, and 575.4±94.8 µm, respectively. The vertical inter-OPL distances were 324.2±93.8 µm, 481.2±104.6 µm, and 494.6±85.0 µm, respectively. Both the horizontal and vertical inter-OPL distances were increased during the follow-up period (P<0.001). Horizontal inter-OPL distances were significantly longer than vertical distances at 1, 2, and 6 months (P<0.001, P<0.001, and P<0.001, respectively). Further nasal and superior elongation was noted on the horizontal and vertical planes in 90.3% and 61.3% of eyes, respectively. The mean degree of asymmetric spreading was significantly associated with an M-score at 6 months postoperatively (P = 0.044) and a difference in M-score between preoperative and 6-month postoperative examinations (P = 0.027). CONCLUSIONS: Elongation of the foveal tissue was noted after MH surgery. This elongation was usually asymmetric, and the degree of asymmetry was associated with postoperative metamorphopsia.

Ultrastructural analysis of in vivo expanded corneal epithelium on amniotic membrane.

The purpose of this study is to characterize and compare the ultrastructural changes occurring during the in vivo cultivation of corneal epithelium on amniotic membrane (AM) at several different time points. Corneal burn patients (n=7) with a corneal epithelial defect and severe limbal damage were selected. Initially, AM transplantation with limbal autograft was performed at the acute stage of corneal burn to reconstruct the damaged ocular surface. One to six (mean interval; 3.3+/-1.2) months later, the central part of AM containing an in vivo expanded corneal epithelium was excised and retransplanted in adjacent lesions. The excised epithelium with AM was examined by electron microscopy and immunohistochemical study. By electron microscopy, one and two months after expansion, cultivated epithelium on AM showed an undifferentiated epithelium and an incomplete basement membrane (BM). But, after three months, the cultivated epithelium began to differentiate into a multilayered epithelium with a continuous BM with increased hemidesmosomes. These findings were further confirmed by immunohistochemical study, that cytokeratin K3 was expressed in the cultivated corneal epithelium and newly formed BM was partially positive of collagen IV at three months. At least 3 months may be needed for the proliferation and differentiation of in vivo cultivated corneal epithelium on AM.

Comparative analysis of the tear protein expression in blepharitis patients using two-dimensional electrophoresis.

Change in the expression of body fluid proteins is caused by many diseases or environmental disturbances. The changes in tear proteins are also associated with various pathological eye conditions. Especially, chronic blepharitis is one of the most common conditions seen in the ophthalmologist's office. However, there are no specific clinical diagnostic tests for blepharitis, and it is difficult to treat effectively. Therefore, the aim of this study was to screen prognostic or diagnostic marker tear proteins for blepharitis and investigate pathogenesis of this disease using proteomics techniques. The tear proteins expressed in patients suffering from blepharitis (patient, n=19) and healthy volunteers (control, n=27) were analyzed using the two-dimensional electrophoresis (2-DE) technique. The differentially expressed proteins in patients were identified with ESI-Q-TOF (electrospray-quadrupole-time-of-flight) mass spectrometry and confirmed with western blotting. Nine proteins in patient were down regulated about 50% compared to those of the control: serum albumin precursor, alpha-1 antitrypsin, lacritin precursor, lysozyme, Ig-kappa chain VIII, prolactin inducible protein (PIP/GCDFP-15), cystatin-SA III, pyruvate kinase, and an unnamed protein. The use of the two-dimensional eletrophoretic technique could give more insight into the disease-related protein expression changes in tear fluids. Our findings reveal that the composition of tear proteins in blepharitis patients is different from that of healthy subjects and may provide further insights into the pathogenesis of blepharitis.