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To evaluate the efficacy of a pigment epithelium-derived factor (PEDF)-derived short peptide 29-mer, on the treatment and prevention of experimental dry eye (EDE).C57BL/6 mice were housed in a low humidity controlled environment chamber for 14 days to induce EDE. The 29-mer was administered topically to their eyes, for treatment or dosing, from the point of housing in the controlled environment chamber. The efficacy of the 29-mer on EDE was evaluated in terms of corneal epithelial integrity, tear secretion, and the density of conjunctival goblet cells. PEDF and inflammatory factors, including tumor necrosis factor-α, IL-1β, IL-6, monocyte chemotactic protein (MCP)-1, matrix metalloproteinase-9, and macrophage infiltration, were examined by real-time polymerase chain reaction, Western blotting, and immunostaining. The involvement of the PEDF receptor/PNPLA2 on the 29-mer effects was evaluated by a specific inhibitor, atglistatin. Rabbit corneal epithelial cells were exposed to hyperosmotic medium to induce inflammatory responses.The levels of PEDF protein increased in the corneal epithelium of EDE, compared with the nonstressed mice. The 29-mer showed a therapeutic effect on EDE and prevented the development of EDE, accompanied by amelioration of the inflammatory factors. The 29-mer effects of inflammatory relief were dramatically reversed by atglistatin. The 29-mer also suppressed the expression of matrix metalloproteinase-9 and proinflammatory cytokines in rabbit corneal epithelial cells induced by hyperosmolarity.Through this animal study, we provide a proof of concept of the anti-inflammatory domain of PEDF having potential to treat dry eye disease.This study shows the 29-mer has novel potential as an ophthalmic drop treatment for dry eye disease.

Background: Intra-articular injection of monoiodoacetate (MIA) has shown to induce extensive chondrocyte degeneration/death in articular cartilage (AC), resulting in destruction of the AC in animals. This has been used often as model of osteoarthritis (OA). Pigment epithelium-derived factor (PEDF) and its derived short peptide 29-mer have been shown to heal tissue injury by activating various types of stem/progenitor cells localized near the lesions. Here we investigated whether the 29-mer is able to evoke chondrogenesis in rats with MIA-injured AC. Methods: AC destruction was induced in Sprague-Dawley rats by a single intra-articular injection of MIA (1 mg) in the right knee. After MIA injection for 7 days, the 29-mer infused with 5% hyaluronic acid (HA) was injected intra-articularly twice, at 4-day intervals. Also, BrdU was injected intraperitoneally into the rats to detect cell proliferation in the damaged AC. The histopathology of AC was determined by hematoxylin and eosin (H&E) staining and Safranin O staining. The regeneration of chondrocytes in the AC was detected by dual-immunostaining of BrdU and chondrocyte markers, including aggrecan, collagen type 2 and Sox9. Changes in hind paw weight distribution were measured to evaluate the MIA-induced joint discomfort. Bone marrow-derived mesenchymal stem cells (MSCs) were used to detect chondrogenic differentiation. The involvement of the PEDF receptor and STAT3 signaling on the 29-mer effects was evaluated using specific inhibitors. Results: MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC, accompanied by the partial recovery of the cartilaginous matrix. The 29-mer/HA also exerted an antinociceptive effect in rats. In culture, the 29-mer promoted chondrogenic differentiation of MSCs with evidence of increased expression of chondrogenic marker genes and proteoglycans, as well as the phosphorylation of STAT3. Pharmacological inhibitors of PEDF-R and STAT3 signaling dramatically blocked the 29-mer effects on cultured MSCs and chondrogenesis in the injured AC. Conclusions: The 29-mer/HA formulation has the ability to stimulate chondrocyte regeneration in the MIA damaged AC. The 29-mer may be a novel agent for the development of future OA treatments.

Cell signaling mediated by the αv integrin plays a pivotal role in macrophage activation in various inflammatory processes, but its involvement in the pathogenesis of dry eye disease (DED) remains unclear. In a murine model of DED, we found increased αv integrin expression in ocular surface macrophages. The αv integrins inhibitor c(RGDfK) ameliorated the corneal damage caused by DED, suggesting a pathogenic role for αv integrin. Because tear hyperosmolarity induces ocular inflammation in DED, a hyperosmolar culture of murine bone marrow-derived macrophages (BMDMs) is used to reproduce inflammation in vitro. However, the expression of proinflammatory cytokine mRNA was minimal, even though αv integrin was induced. In searching for components that are involved in αv integrin-mediated inflammation but that are missing from the culture model, we showed that the levels of vitronectin (VTN), a binding ligand of αv integrins, were increased in the tear fluid and conjunctival stroma of DED animals. The addition of VTN prominently enhanced hyperosmolarity-induced inflammation in BMDMs. Mechanistically, we showed that VTN/αv integrins mediated NF-κB activation to induce inflammatory gene expression in the BMDMs. Our findings indicate that interaction the of VTN with αv integrins is a crucial step in the inflammatory process in DED and suggests a novel therapeutic target.

Purpose To investigate the potential of a pigment epithelium-derived factor (PEDF) peptide 44-mer to promote nerve regeneration in a rabbit corneal nerve injury model to demonstrate its neurotrophic ability in cultivated mouse trigeminal neuron cells. Methods Subconjunctival or intrastromal injection of 44-mer on the cornea was performed in a rabbit model of corneal nerve injury created by corneal epithelial debridement. Immunocytochemical analysis (44-mer, anti-tubulin III, SMI312, CD11b, and α-SMA) and in vivo confocal microscopy were performed. Corneal sensation was estimated using a Cochet-Bonnet corneal esthesiometer. Primary cultivated mouse trigeminal neurons were used to examine the in vitro neurotrophic ability of 44-mer. The cellular morphology and the immunocytochemical staining with anti-tubulin III and SMI312 in different concentrations of 44-mer were compared, and a quantitative assessment of neurite outgrowth was performed. Results Immunohistochemical staining showed the retention of 44-mer in the corneal stroma for at least 7 days after a single dose of corneal intrastromal injection and promoted corneal nerve regeneration revealed by in vivo confocal microscopy. Corneal esthesiometer demonstrated gradual recovery of the corneal sensation in 44-mer-treated eyes with a lower corneal touch threshold than wounded vehicles and closer to baseline at 3 weeks after corneal injury (P < 0.001). In vitro studies showed a dose-dependent neurotrophic effect of 44-mer in cultivated trigeminal neuron cells. Conclusions The 44-mer showed in vivo and in vitro corneal neurotrophic abilities. Our results suggest that intrastromal injection of 44-mer into the corneal stroma may have a potential role in treating diseases related to corneal nerve damage.

Purpose To describe the efficacy of autologous serum (AS) eye drops to reverse severe contact lens (CL)-induced limbal stem cell (LSC) deficiency (LSCD). Methods This is a prospective, uncontrolled, interventional case series that enrolled 20 eyes of 14 consecutive patients diagnosed with severe CL-induced LSCD at presentation, based on clinical examination, at a tertiary referral center for the period December 2016 to December 2018. All eyes underwent AS treatment for at least 2 weeks with a follow-up for at least 2 months. Demographic data and treatment outcomes were collected and analyzed. Results The mean patient age at presentation was 30.5 years (range, 19-49 years). The mean duration of soft contact lens wear was 15.6 years (SD, 7.58 years; range, 5-31 years). All study eyes had pain and blurred vision at presentation. All eyes had recurrent or persistent corneal epithelial defect, stromal scarring and opacity, and superficial vascularization and peripheral pannus at presentation. Aggressive treatment with AS succeeded in all eyes. Signs and symptoms of LSCD stabilized in all eyes within 2 weeks and resolved in 6 eyes (30.0%) in 2 weeks, 9 eyes (45.0%) in 4 weeks, and 5 eyes (25.0%) in 8 weeks. The mean follow-up time was 9.45 ± 1.79 weeks (range, 8-24 weeks). Conclusions Early identification and aggressive treatment of the ocular surface disease with AS can medically reverse severe CL-induced LSCD and prevent the need for surgical intervention.

Highlights • We report a case of intramuscular hemangioma mimicking osteoid osteoma. • Magnetic resonance image (MRI) is the most precise diagnostic tool for the identification of soft-tissue mass adjacent to the bone. • Precise preoperative diagnosis is essential to avoid excessive surgery., Introduction Intramuscular hemangioma in the periosteal region is rare. Although comprising less than 1% of all hemangiomas, they represent the most common type of intramuscular tumors. When located adjacent to bone, a periosteal reaction can occur. The deep localization of the hemangioma poses the diagnosis difficult. Only 8% to 19% of cases were diagnosed before surgery according to the literature review. Presentation of case We present a case of forty-one-year-old female diagnosed with intramuscular hemangioma, mimicking osteoid osteoma, adjacent to the periosteal region of tibia diaphysis treated by surgical excision. Discussion When intramuscular hemangioma occurs nearby a bone structure, it can cause cortical, medullary and periosteal bone changes that are frequently misdiagnosed by plain radiography. Due to their infrequency, deep location, and atypical presentation, these lesions are seldom diagnosed at presentation. The hemangioma of the periosteal region can be locally destructive due to compression exerted on neighboring structures. It does not regress spontaneously, and surgical excision is frequently needed. Conclusion Intramuscular hemangioma of periosteal region occurs most commonly adjacent to long bones of the lower limb. They can cause hypertrophic periosteal reactions mimicking a periosteal or parosteal tumor. Although osteoid osteoma was considered in the differential diagnosis, MRI with enhancement should be performed to exclude intramuscular hemangioma. This may avoid unnecessary aggressive en-bloc tumor excisions resulting in bone weakness and prolonged rehabilitation. This case report has been written in line with the SCARE criteria (Agha et al., 2016 [1]).

Psoriasis is a chronic inflammatory skin disease characterized by excessive growth of keratinocytes and hyperkeratosis in the epidermis. An abnormality of the non-lesional epidermis at an early stage of psoriasis is involved in triggering inflammatory cell infiltration into the dermis. Integrin &alpha, 5&beta, 1 acts as a receptor for fibronectin and has been found to be overexpressed in non-lesional psoriatic epidermis. To investigate whether &alpha, 1 integrin has a potential as a drug target for psoriasis treatment, the &alpha, 1 integrin-binding peptide, C16, was used to obstruct the HaCat keratinocyte cellular responses induced by fibronectin (Fn) in culture and psoriasis-like skin inflammation induced in mice by imiquimod (IMQ). The C16 exhibited antagonistic activity against &alpha, 1 integrin in HaCat cells, with evidence of suppression of the Fn-mediated proliferative, cytoskeletal, and inflammatory responses. Topical treatment with C16 greatly reduced the IMQ-induced epidermal hyperplasia, infiltration of neutrophils/macrophages, and expression of pro-inflammatory mediators in mouse skin. The C16SP (C16-derived short peptide, DITYVRLKF) also exhibited antagonistic activity, suppressing &alpha, 1 integrin activity in culture, and reducing IMQ-induced skin inflammation. Taken together, this study provides the first evidence that &alpha, 1 integrin may be a potential drug target for psoriasis. The synthetic C16 peptide may serve as an agent for psoriasis therapy.

Background Tendon stem/progenitor cells (TSPC) exhibit a low proliferative response to heal tendon injury, leading to limited regeneration outcomes. Exogenous growth factors that activate TSPC proliferation have emerged as a promising approach for treatment. Here, we evaluated the pigment epithelial-derived factor (PEDF)-derived short peptide (PSP; 29-mer) for treating acute tendon injury and to determine the timing and anatomical features of CD146- and necleostemin-positive TSPC in the tendon healing process. Methods Tendon cells were isolated from rabbit Achilles tendons, stimulated by the 29-mer and analyzed for colony-forming capacity. The expression of the TSPC markers CD146, Oct4, and nestin, induced by the 29-mer, was examined by immunostaining and western blotting. Tendo-Achilles injury was induced in rats by full-thickness insertion of an 18-G needle and immediately treated topically with an alginate gel, loaded with 29-mer. The distribution of TSPC in the injured tendon and their proliferation were monitored using immunohistochemistry with antibodies to CD146 and nucleostemin and by BrdU labeling. Results TSPC markers were enriched among the primary tendon cells when stimulated by the 29-mer. The 29-mer also induced the clonogenicity of CD146+ TSPC, implying TSPC stemness was retained during TSPC expansion in culture. Correspondingly, the expanded TSPC differentiated readily into tenocyte-like cells after removal of the 29-mer from culture. 29-mer/alginate gel treatment caused extensive expansion of CD146+ TSPC in their niche on postoperative day 2, followed by infiltration of CD146+/BrdU− TSPC into the injured tendon on day 7. The nucleostemin+ TSPC were located predominantly in the healing region of the injured tendon in the later phase (day 7) and exhibited proliferative capacity. By 3 weeks, 29-mer-treated tendons showed more organized collagen fiber regeneration and higher tensile strength than control tendons. In culture, the mitogenic effect of the 29-mer was found to be mediated by the phosphorylation of ERK2 and STAT3 in nucleostemin+ TSPC. Conclusions The anatomical analysis of TSPC populations in the wound healing process supports the hypothesis that substantial expansion of resident TSPC by exogenous growth factor is beneficial for tendon healing. The study suggests that synthetic 29-mer peptide may be an innovative therapy for acute tendon rupture.

Purpose: To investigate the distribution of corneal and ocular spherical aberrations (SAs) in eyes with cataract in the Taiwanese population. Methods: Corneal and ocular SAs were measured in the central 6-mm optical zone using wavefront aberrometry. Axial length (AL) and keratometry (K) were also evaluated in each eye. Results: A total of 413 eyes in 234 patients were analyzed. The mean age of the patients was 66.8 ± 10.64 years. The mean AL and K values were 24.32 mm and 44.08 D, respectively. The mean corneal SA was 0.307 ± 0.135 μm and ocular SA was −0.042 ± 0.487 μm. Ocular and corneal SAs were significantly correlated (r2 = 0.04, p < 0.001). Corneal and ocular SAs were not significantly correlated with K (p = 0.096 and p = 0.634, respectively), but were significantly correlated with AL (p < 0.001). Multilinear regression showed that corneal SAs and age were the dependent variables that predicted ocular SAs (r2 = 0.143, F = 13.65, p < 0.01), especially in patients who were aged > 50 years, for whom a strongly significant positive correlation was found (r2 = 0.102, F = 11.10, p < 0.001). Conclusion: Corneal and ocular SAs varied among cataract patients and correlated with AL. After 50 years of age, ocular SAs increased significantly because of an increase in internal (lenticular) SAs. Corneal SAs in Taiwanese patients were larger than those in Japanese patients and similar to those in Chinese and Malaysian populations. Preoperative measurement of wavefront aberrations is necessary to select which aspherical intraocular lenses are most suitable for achieving better postoperative visual quality.

This study aims to report our experience of using fluid-ventilated, gas-permeable scleral contact lenses (SCLs) for visual rehabilitation of patients with keratoconus and irregular astigmatism after refractive surgery. This is a noncomparative interventional case series reporting eight consecutive patients fitted with SCLs because of irregular astigmatism following the failure of other optical corrections. Retrospective chart review and data analysis included age, sex, etiology prior to lens fitting, visual outcomes, follow-up time, and complications. Twelve eyes of eight patients were studied. All eyes were fitted with SCLs due to unsatisfactory vision with spectacle correction or other contact lens modalities. Five eyes had keratoconus and seven had irregular corneas post refractive surgery. The mean follow-up period was 14.4 ± 1.3 months (range 11–17 months). The mean age was 32.63 ± 7.68 years (range 18–48 years). The average steepest keratometry(Kmax) of our series was 49.56 ± 12.2 D. The mean refractive astigmatism was 5.50 ± 5.3 D. The mean best corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution improved from 0.71 ± 0.50 (range 0.10–1.40) to 0.05 ± 0.07 (range 0.00–0.15) after SCL fitting (p < 0.001). All reported eyes achieved significant improvement in the BCVA with SCL fitting. None of the patients discontinued to wear SCLs. SCLs should be considered lenses of choice in irregular corneas refractory to conventional optical correction.

To investigate the differences in hemorheological parameters between patients with normal tension glaucoma (NTG) and normal controls.Twenty patients with NTG and 21 age-matched normal controls were included in the study. Hemorheological parameters of the venous blood samples, including blood viscosity at the shear rates of 500, 250, and 5 s(-1), and viscoelasticity were measured using a rotational rheometer; erythrocyte deformability and aggregation were measured using a ektacytometer; and erythrocyte rigidity and the oxygen transport efficiency of blood were calculated.Higher blood viscosities at the high (p 0.01), medium (p 0.01), and low (p 0.01) shear rates were found in the NTG group than in the control group. Significantly higher erythrocyte aggregation index (p 0.01); lower index of erythrocyte deformability at medium (p 0.01) and high shear rates (p 0.05); and lower oxygen transport efficiency of blood at low (p 0.01), medium (p 0.01), and high shear rates (p 0.05) were obtained in the NTG group.The higher blood viscosity of the NTG patients at the high shear rate may be related to impaired erythrocyte deformability associated with a change in erythrocyte rigidity. Higher blood viscoelasticity and blood viscosity of NTG patients at the low shear rate was due to increased erythrocyte aggregability. Also, the impaired erythrocyte deformability of NTG patients is susceptible to developing abnormalities of the distal microcirculation. Furthermore, the increased blood viscosity and low oxygen transport efficiency of blood may result in hypoperfusion of optic nerve in NTG patients.

Purpose: To report the surgical outcome of pars plana vitrectomy (PPV) without internal limiting membrane (ILM) peeling in three highly myopic patients with macular retinoschisis and associated posterior staphyloma. Methods: We report three highly myopic patients with macular retinoschisis and foveal detachment who underwent simple PPV without ILM peeling, with long-acting gas tamponade. Main outcome evaluations included best corrected visual acuity, biomicroscopic appearance and optical coherence tomography findings. Results: Pars plana vitrectomy without ILM peeling resulted in anatomic and functional improvement in all three operated eyes for follow-up periods of ≥ 12 months. Conclusions: Pars plana vitrectomy without ILM peeling is effective for treating macular retinoschisis and foveal detachment in highly myopic eyes with posterior staphyloma. Visual and anatomic outcomes are comparable with those in previous studies in which ILM removal was performed.

OBJETIVO: Avaliar possíveis erros na administração de drogas intravítreas para o tratamento da endoftalmite e propor técnica que seja reprodutível e acessível. MÉTODOS: Avaliação de técnicas utilizadas e aferição dos volumes retidos nas agulhas utilizando balança analítica. RESULTADOS: A média e o desvio padrão dos volumes retidos nas agulhas de 26, 22 (25 x 0,7 mm e 30 x 0,7 mm) e 18 G (gauge) foram 0,051±0,006, 0,056±0,005, 0,055±0,004 e 0,075±0,004, respectivamente, para a marca Ryncos® e 0,050±0,003, 0,056±0,002, 0,063±0,002 e 0,084±0,004, respectivamente, para a marca Becton-Dickinson®. Houve diferença estatisticamente significante entre os volumes retidos das duas marcas para as agulhas de 26, 22 (30 x 0,7 mm) e 18 G com p = 0,01, p < 0,01 e p < 0,01 respectivamente. Não foi encontrada diferença estatisticamente significante apenas para as agulhas de 25 x 0,7 mm (22 G) com p= 0,83. CONCLUSÃO: A maioria das agulhas utilizadas na injeção intravítrea comporta um volume residual no espaço morto que deve ser valorizado, minimizando assim erros na injeção de drogas intravítreas no tratamento da endoftalmite.PURPOSE: To assess evaluate the accuracy of intravitreal drug administration in the treatment of endophthalmitis and to suggest a reproducible and accessible technique for this procedure. METHODS: To assess the retained volumes in needles used for the intravitreal injection of antibiotics using an analytical scale. RESULTS: Means and standard deviations of retained volumes in the 26, 22 ( 25 x 0.7 mm and 30 x 0.7 mm ) and 18 G were respectively 0.051±0.006, 0.056±0.005, 0.055±0.004 and 0.075±0.004 for needles Ryncos® and 0.050±0.003, 0.056±0.002, 0.063±0.002 and 0.084±0.004 for Becton-Dickinson®. There were statistically significant differences in the retained volumes between the two needle brands for 26, 22 (30 x 0.7 mm) and 18 G needles with p = 0.01, p < 0.01 and p < 0.01 respectively. No difference was found only for 25 x 0.7 mm 22 G needle with p = 0.83. CONCLUSION: Most needles used for intravitreal injection hold a retained volume in the reserve needle compartment that should be considered during the injection technique, therefore minimizing errors during intravitreal injection of antibiotics.

OBJETIVO: Avaliar possíveis erros na administração de drogas intravítreas para o tratamento da endoftalmite e propor técnica que seja reprodutível e acessível. MÉTODOS: Avaliação de técnicas utilizadas e aferição dos volumes retidos nas agulhas utilizando balança analítica. RESULTADOS: A média e o desvio padrão dos volumes retidos nas agulhas de 26, 22 (25 x 0,7 mm e 30 x 0,7 mm) e 18 G (gauge) foram 0,051±0,006, 0,056±0,005, 0,055±0,004 e 0,075±0,004, respectivamente, para a marca Ryncos® e 0,050±0,003, 0,056±0,002, 0,063±0,002 e 0,084±0,004, respectivamente, para a marca Becton-Dickinson®. Houve diferença estatisticamente significante entre os volumes retidos das duas marcas para as agulhas de 26, 22 (30 x 0,7 mm) e 18 G com p = 0,01, p < 0,01 e p < 0,01 respectivamente. Não foi encontrada diferença estatisticamente significante apenas para as agulhas de 25 x 0,7 mm (22 G) com p= 0,83. CONCLUSÃO: A maioria das agulhas utilizadas na injeção intravítrea comporta um volume residual no espaço morto que deve ser valorizado, minimizando assim erros na injeção de drogas intravítreas no tratamento da endoftalmite.

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.

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 ( 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. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Purpose To report the in vivo confocal microscopy (CM) findings of a patient with combined pre-Descemet membrane corneal dystrophy and Fuchs endothelial dystrophy. Methods A 38-year-old woman with pre-Descemet membrane corneal dystrophy and Fuchs endothelial dystrophy was studied. Routine ophthalmic examination, standard slit-lamp biomicroscopy, pachymetry, and in vivo CM analysis of the morphology of the corneal epithelium, subbasal nerves, stroma, and endothelium were performed. Results Biomicroscopy revealed bilateral corneal guttae with central corneal edema, beaten metal appearance, and pigment dusting of the endothelium. Numerous tiny pleomorphic opacities located in the deep stroma immediately anterior to Descemet membrane were evidenced in both eyes. In vivo CM showed numerous pleomorphic and highly reflective small particles in the cytoplasm of keratocytes in the deep stroma adjacent to the corneal endothelial layer. No abnormalities could be detected in the epithelial layer and in the midstromal layer. In the endothelial layer, there were multifocal hyporeflective areas with occasional central highlight among hyperreflective endothelial cells. The ultrasonic pachymetry showed corneal thicknesses of 652 and 628 μm in the right eye and in the left eye, respectively. Conclusions In vivo CM is a powerful tool in the study of rare corneal dystrophies and degenerations and nonprogressive or slowly progressive corneal disorders where there is a limited availability of corneal tissue for examination and when the final diagnosis is difficult to obtain with conventional methods.

To determine whether matrix metalloproteinase-7 (MMP-7) that is stably overexpressed by mouse corneal fibroblast cell lines exhibits proteolytic activity against the NC1 fragment of collagen XVIII.Corneal fibroblasts isolated from MMP-7 knockout (7ko) mice were subjected to SV40 T-antigen immortalization and stably transfected with a bicistronic retroviral vector encoding green fluorescence protein and active MMP-7. The resulting MMP-7 knock-in fibroblasts (7ko-MMP-7 cells) were isolated and enriched by fluorescence activated cell sorting (FACS). Culture media samples from 7ko and 7ko-MMP-7 cells were then incubated with the recombinant NC1 fragment of collagen XVIII, and NC1 degradation was monitored by immunoblotting.Immunoblot analysis revealed that MMP-7 was present in lysates and culture media from 7ko-MMP-7 fibroblasts, but not media from immortalized 7ko fibroblasts. Importantly, lower amounts of the NC1 fragment were present in in vitro enzymatic reaction mixtures containing concentrated 7ko-MMP-7 media than in those containing concentrated 7ko media.Immortalized fibroblasts stably transfected with MMP-7 secrete active MMP-7 with proteolytic activity towards the NC1 fragment of collagen XVIII.

BACKGROUND AND OBJECTIVE: To report computer-assisted image processing for a simulated stereo effect of fundus and fluorescein angiography (FAG) digital photographs in patients with ocular fundus pathology. PATIENTS AND METHODS: Fundus red-free and FAG photographs of patients with a variety of ocular fundus pathologies were digitized and then processed with the sketch bas relief filter of Adobe Photoshop software (Adobe Systems, San Jose, CA) to create a stereo-like carved image. The images were compared with indirect slit-lamp biomicroscopy and optical coherence tomography (OCT) for accuracy and reliability in showing ocular pathology. RESULTS: The bas relief filter could transform ocular fundus and FAG photographs into images carved in relief. Dark areas of the fundus image took on the background color, and light colors used the foreground color. A variety of ocular fundus pathologies with fluorescein dye leakage in the FAG were found to be elevated lesions after image processing with the bas relief filter. Image misinterpretations might occur and can be avoided with careful examination of the ocular fundus with indirect slit-lamp biomicroscopy and OCT. CONCLUSION: Computer-assisted image processing for a simulated stereo effect of fundus and FAG photographs is a simple and assessable method of image processing that decreases the complexity of ocular fundus and FAG photographs for patient interpretation. It might be a useful tool in assisting physician–patient communication by creating pseudo three-dimensional images and highlighting ocular fundus pathology. [Ophthalmic Surg Lasers Imaging 2010;41:293–300.]

Background and Objective:To investigate inaccuracy and variability in residual stromal thickness estimation in LASIK by pachymetry and measurements of corneal thickness, flap thickness, and ablation depth.Patients and Methods:In 73 eyes of 37 patients, preoperative and postoperative corneal thicknesses were obtained with slit-scanning elevation topography and the ultrasound pachymeter. LASIK was performed and corneal flaps were created with a microkeratome. Flap thickness and ablation depth (expected and achieved) were calculated. Residual stromal thickness estimation error was analyzed.Results:The mean preoperative corneal thicknesses were 559.58 ± 23.47 and 554.92 ± 29.95 μm for the ultrasound pachymeter and slit-scanning elevation topography, respectively. Measurement differences ranged from −36 to 30 μm. With the pachymeter, calculated mean flap thickness was 139.58 ± 17.59 μm. With this device, predicted ablation depth differed from achieved depth by 20% or more in approximately one-third (30.14%) of treated patients; ablation differences ranged from 10.0% to 19.99% in 37% of patients and 1.00% to 9.99% in 31.5% of patients.Conclusion:Imprecision of microkeratome cuts, preoperative corneal pachymetry, and laser ablation depth have a significant impact on the inaccuracy of residual stromal thickness prediction. Especially in patients with borderline corneal thickness, intraoperative pachymetry measurements and a residual stromal thickness higher than the safety margin of 250 μm are recommended to minimize iatrogenic ectasia.

To evaluate the effect of subconjunctival injection of recombinant adeno-associated virus (rAAV)-angiostatin in alkali burn-induced corneal angiogenesis.Adeno-associated viral vector-mediated gene delivery into extraocular tissue was determined by fluorescent microscopy three weeks after subconjunctival injection of viral vector expressing green fluorescent protein (rAAV-GFP). Subconjunctival injection of recombinant adeno-associated viral vector expressing human angiostatin (rAAV-angiostatin) and blank rAAV viral vector (control) was performed in the left eye of male Sprague-Dawley rats (n=6). Alkaline induction of corneal neovascularization (NV) was performed three weeks later. Corneal NV regression was analyzed 7-14 days after alkali burn with slit lamp and digital pictures. Transgenic expression of angiostatin in the cornea, conjunctiva, retina, and muscle insertions was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR).Transgenic GFP gene expression was detected mainly in the muscle fibers at the extraocular muscle (EOM) insertions after subconjunctival injection. The area of corneal neovascularization was significantly lower in eyes injected with rAAV-angiostatin (p0.01) than in eyes injected with the control virus. RT-PCR demonstrated that the angiostatin gene expression was highly detectable in muscle fibers and not detectable in the conjunctiva, cornea, and retina.Subconjunctival injection of rAAV-angiostatin reduced alkali burn-induced corneal angiogenesis. We proved the concept that ocular gene therapy by subconjunctival injection of adenovirus-associated gene transfer of angiogenesis inhibitors can be a simple and safe treatment modality that can achieve therapeutic levels and long lasting effects in the treatment of corneal NV induced by ocular surface disorders.

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.

The possibility of achieving supernormal vision in terms of acuity and contrast has fueled the imagination and creativity of vision researchers to pursue the goal of customized wavefront refractive surgery. This goal is achieved by generating an optimal ablation pattern based on individual anatomical and functional characteristics of the treated eye. However, increasing concerns regarding the clinical applicability of customized wavefront correction have emerged, and the possibility of achieving supernormal vision in all patients has been challenged. It is by understanding current optical, physiologic,and technological challenges faced by treating physicians and basic researchers that we can develop clear objectives for the future development of customized refractive surgery.