Hsiao-Sang Chu

Subconjunctival injection of bevacizumab in the treatment of corneal neovascularization associated with lipid deposition.

Purpose: To determine the effects on corneal neovascularization (NV) and lipid deposition after subconjunctival injection of bevacizumab in patients who had NV associated with lipid keratopathy. Methods: A case interventional study enrolled 18 patients (18 eyes) with lipid keratopathy. We gave monthly subconjunctival injections of bevacizumab from 3 to 10 times during the follow-up period according to the clinical response. We evaluated the centricity, extent, and percentage of involved corneal surface (PICS) of the corneal NV; the density and PICS of the corneal lipid deposition; and best-corrected visual acuity before and after treatment. We analyzed the treatment effects using Wilcoxon and Student t tests. Results: After the treatment, the change in best-corrected visual acuity was less than 2 lines. The extent, centricity, and PICS of the corneal NV and the density and PICS of the corneal lipid deposition decreased significantly after treatment (P = 0.014/0.002/0.001 and 0.001/<0.001, respectively). No eyes had side effects. Conclusions: The effects of subconjunctival injection of bevacizumab in treating corneal NV associated with lipid deposition were significant in some patients.

The different effects of early and late bevacizumab (Avastin) injection on inhibiting corneal neovascularization and conjunctivalization in rabbit limbal insufficiency.

PURPOSE To compare the effects of early, mid, and late subconjunctival injection of bevacizumab on corneal neovascularization (NV) and conjunctivalization in a rabbit limbal insufficiency model. METHODS Limbal insufficiency was created surgically, and subconjunctival injections of 2.5 mg bevacizumab twice weekly for 1 month were started immediately (early group), 1 week (mid group), and 1 month after injury (late group). The corneal epithelial alterations, stromal opacity, centricity, extent, and PICS (percentage of involved corneal surface) of the corneal NV were evaluated. The expression of cytokeratins K3, K4, K12, K13, and MUC5 by the corneal surface cells was examined by immunohistochemistry. RESULTS Bevacizumab significantly inhibited corneal NV in the early and mid, but not the late, treatment groups at 4 weeks after treatment (PICS: P < 0.01 in the early group, P < 0.01 in the mid group, and P > 0.05 in the late group). Early and mid treatment produced significant inhibition of corneal alteration (P < 0.01 in the early group and P = 0.03 in the mid group) and stromal opacity (P < 0.01 in the early group and P = 0.02 in the mid group) at 4 months after treatment but not in the late group. The immunohistochemistry of cytokeratin on the corneal surface cells at 1 month after treatment was K3(+), K4(-), K12(+), K13(-), and MUC5(-) in the early group; K3(+), K4(+), K12(+), K13(+), and MUC5(-) in the mid group; and K3(+), K4(+), K12(-), K13(+), and MUC5(+) in the late treatment group. CONCLUSIONS Early and mid bevacizumab injection inhibited corneal NV, epithelial alteration, and stromal opacity in limbal insufficiency, but late treatment did not. Early treatment with bevacizumab seems to be clinically beneficial in the management of limbal injury such as chemical burn.

Non-tuberculous mycobacterial keratitis

Non-tuberculous mycobacteria are environmental, opportunistic pathogens that are increasingly being recognized as important causes of many human diseases. Among them, rapidly growing mycobacteria are the most notorious organisms causing infectious keratitis. Non-tuberculous mycobacterial (NTM) keratitis commonly occurs after trauma or refractive surgery, and can masquerade as fungal, herpetic or amoebic keratitis. Therefore, the diagnosis is often delayed. Prolonged medical treatment and judicious surgical debridement are required in order to eradicate the pathogens. Combination therapy with aminoglycosides, macrolides and fluoroquinolones improves the prognosis and decreases the occurrence of drug resistance. However, regardless of the development of new diagnostic techniques and antimicrobials, NTM keratitis remains a clinical challenge for most ophthalmologists. In this article, we provide a concise introduction to the epidemiological features and clinical characteristics of NTM keratitis, and the modern diagnostic tools used for it. We also summarize the current concepts of prevention and treatment for this potentially devastating condition.

Anterior corneal buttons from DSAEK donor tissue can be stored in optisol GS for later use in tectonic lamellar patch grafting.

Purpose: The aim of this study was to evaluate the feasibility of storing anterior corneal buttons split from donor Descemet stripping automated endothelial keratoplasty (DSAEK) tissue for later use in tectonic lamellar patch grafting. Methods: Donor corneas for DSAEK were split into anterior and posterior lamellae using a 350-&mgr;m depth microkeratome, and the remaining anterior corneal buttons were stored for up to 4 weeks at 4°C in Optisol GS before use in patch grafting of the cornea and sclera. Results: Optisol GS–preserved anterior lamellar patch grafts successfully restored and maintained corneoscleral integrity after the removal of limbal dermoids (5 cases), after the coverage of the exposed polypropylene suture ends of scleral fixated posterior chamber intraocular lenses (2 cases), corneoscleral melting after pterygium excision (3 cases), sterile corneal ulceration with or without perforation (5 cases), Mooren ulceration (3 cases), and pseudomonas corneal ulceration with impending perforation (1 case). It was also used as a temporary substitute while waiting for a full-thickness corneal graft in a fulminant candida infection after DSAEK (1 case). All grafts remained structurally intact at the last postoperative examination of 19.2 ± 7.6 months after the tectonic surgery. Conclusions: Anterior corneal buttons from DSAEK donor tissue may be stored in Optisol GS for later use in tectonic patch grafting. This method obviates the longer operating time required for the surgeon to manually dissect the donor cornea in the operating room and reduces the wastage of precious donor corneas in countries where there are chronic shortages of eye bank donor tissue.

Correlation of Pseudomonas aeruginosa genotype with antibiotic susceptibility and clinical features of induced central keratitis.

PURPOSE To determine the association of type III secretion system (T3SS) genotype with antibiotic susceptibility, serotypes, and clinical manifestation of centrally located Pseudomonas aeruginosa keratitis. METHODS Clinical characteristics of P. aeruginosa keratitis cases from 2001 to 2011 were analyzed. Each strain was serotyped and genotyped for T3SS exotoxin genes. Antibiotic sensitivity and minimum inhibitory concentrations were determined with agar dilution method. Prognostic factors affecting final visual outcomes and time to re-epithelialization were analyzed using linear and Cox regression models. RESULTS Forty-four invasive and 28 cytotoxic strains were identified. Invasive strains occurred mostly in males (P = 0.03) with older age (P = 0.009) and ocular surgery or trauma history (P = 0.006), poor presenting (P = 0.04) and final (P < 0.0001) best spectacle-corrected visual acuity (BSCVA), and larger infiltration size (P = 0.03). Cytotoxic strains were associated with contact lens wear (P < 0.0001). Poor prognostic factors for final BCVA after adjusting for sex, age, and contact lens wear included invasive strains (P = 0.02), larger infiltration area (P = 0.02), deeper infiltrations (P = 0.02), and presence of hypopyon (P = 0.09). Factors affecting complete re-epithelialization time included invasive strains (P = 0.02), infiltration area (P = 0.01), depth (P = 0.02), and hypopyon (P = 0.03) after adjusting for age and sex. Serotypes 2, 6, and 11 were more commonly found among all isolates. A trend to increased fluroquinolone resistance is noted for invasive strains, although not reaching statistically significant difference. CONCLUSIONS Cytotoxic strains are associated with contact lens wear while invasive strains are related to poor prognosis and increased resistance to fluoroquinolones. Clinicians should be aware of the two different genotypes of P. aeruginosa affecting prognosis.

Nontuberculous mycobacterial ocular infections--comparing the clinical and microbiological characteristics between Mycobacterium abscessus and Mycobacterium massiliense.

Purpose To analyze the clinical characteristics of nontuberculous mycobacterial (NTM) ocular infections and the species-specific in vitro antimicrobial susceptibility. Material and Methods In 2000 to 2011 at the National Taiwan University Hospital, multilocus sequencing of rpoB, hsp65 and secA was used to identify NTM isolates from ocular infections. The clinical presentation and treatment outcomes were retrospectively compared between species. Broth microdilution method was used to determine the minimum inhibitory concentrations of amikacin (AMK), clarithromycin (CLA), ciprofloxacin (CPF), levofloxacin (LVF), moxifloxacin (MXF) and gatifloxacin (GAF) against all strains. The activities of antimicrobial combinations were assessed by the checkerboard titration method. Results A total of 24 NTM strains (13 Mycobacterium abscessus and 11 Mycobacterium massiliense) were isolated from 13 keratitis, 10 buckle infections, and 1 canaliculitis cases. Clinically, manifestations and outcomes caused by these two species were similar and surgical intervention was necessary for medically unresponsive NTM infection. Microbiologically, 100% of M. abscessus and 90.9% of M. massiliense ocular isolates were susceptible to amikacin but all were resistant to fluoroquinolones. Inducible clarithromycin resistance existed in 69.3% of M. abscessus but not in M. massiliense isolates. None of the AMK-CLA, AMK-MXF, AMK-GAF, CLA-MXF and CLA-GAF combinations showed synergistic or antagonistic effect against both species in vitro. Conclusions M. abscessus and M. massiliense are the most commonly identified species for NTM ocular infections in Taiwan. Both species were resistant to fluoroquinolones, susceptible to amikacin, and differ in clarithromycin resistance. Combined antimicrobial treatments showed no interaction in vitro but could be considered in combination with surgical interventions for eradication of this devastating ocular infection.

Recurrence of corneal neovascularization associated with lipid deposition after subconjunctival injection of bevacizumab.

Purpose: To report 7 cases of recurrent corneal neovascularization (NV) and lipid deposition after subconjunctival injection of bevacizumab for the treatment of corneal NV–induced lipid keratopathy. Methods: We conducted a prospective interventional case series that included 20 eyes of chronic lipid keratopathy that received bevacizumab injection for the treatment of corneal NV and lipid deposition, including 7 eyes with recurrent corneal NV and lipid deposition after ceasing treatment. Repeated subconjunctival injections of bevacizumab were performed in 5 patients with recurrence. Penetrating keratoplasty was performed in 1 patient who had severely recurrent lipid deposition. Clinical presentation of corneal NV and lipid deposition, best-corrected visual acuity, and complications after treatments were recorded. Results: Bevacizumab inhibited corneal NV and lipid depositions in 19 patients. Seven of the 20 patients (35%) had different patterns of recurrence of corneal NV/lipid deposition 6 to 15 months after discontinuing treatment. Five of the 7 patients in whom corneal NV/lipid deposition was recurrent received another course of repeated bevacizumab treatments. Three eyes had partial response to the second course of treatment. Two eyes had too short re-treatment course to have conclusions. One patient who received penetrating keratoplasty had successful result after surgery. Conclusions: Corneal NV and lipid deposition may recur after ceasing the subconjunctival bevacizumab injections for lipid keratopathy. Some patients respond at least partially to repeated injections.

Bevacizumab for the Treatment of Corneal Neovascularization

Corneal neovascularization (NV) is a severe complication associated with inflammatory or infectious disorders of the cornea. NV may lead to severe reduction in visual acuity and poor prognosis for corneal transplantation and excimer laser refractive surgery. Vascular endothelial growth factor (VEGF), a potent angiogenic factor, has been reported to play a major role in the pathogenesis of corneal NV. Use of an anti-VEGF antibody would seem a theoretically plausible means for treating corneal NV. Recently, bevacizumab, a humanized monoclonal antibody against VEGF, has been reported significantly to inhibit choroidoretinal NV. Several animal and human studies have also reported beneficial effects of bevacizumab against corneal NV; both topical and subconjunctival application were effective. Nonetheless, optimal dosage, route of administration, and possible complications are yet to be fully characterized. This review summarizes the relevant literature and formulates several key questions to guide future use of bevacizumab in the treatment of corneal NV.

Recurrent advancing wavelike epitheliopathy from the opposite side of the initial presentation.

Purpose: To report an unusual case of advancing wavelike epitheliopathy that recurred at a site opposite to the initially affected site. Methods: Single interventional case report. This report describes a 50-year-old woman who presented with advancing, wavelike epitheliopathy of her right eye that lasted 2 months. Results: Slit-lamp biomicroscopy revealed wavy, coarse, irregular epithelium extending from the upper limbus to the central cornea. Confocal microscopy revealed abnormal basal epithelial cells with a loss of cellular borders and hyperreflective nuclei. Application of 1% silver nitrate solution onto the superior limbus effectively treated this condition. However, wavy, irregular epithelium was observed 2 years later in the lower limbus. Conclusions: Advancing wavelike epitheliopathy can occur from the lower limbus and recur from the opposite side of the initial presentation, even after successful treatment with 1% silver nitrate solution.

Change of Recipient Corneal Endothelial Cells After Non-Descemet's Stripping Automated Endothelial Keratoplasty in a Rabbit Model

PURPOSE We used a rabbit model to evaluate the interface embedded between the recipient corneas and transplanted donor corneal discs after non-Descemets stripping automated endothelial keratoplasty (nDSAEK). METHODS Unilateral DSAEK and nDSAEK surgeries were performed on New Zealand white rabbits. In vivo confocal microscopy was performed to show: the changes in corneal endothelial cells embedded between the recipient corneas and the transplanted donor corneal discs (CEEB); and the interface opacity by z profile. Immunohistochemistry were performed to evaluate the functional change of CEEB at post-nDSAEK 3 months. Transmission electron microscopy was performed to evaluate the morphology of CEEB after nDSAEK at post-nDSAEK 1, 3, and 6 months. RESULTS In vivo confocal microscopy showed a time-dependent decrease in the density of CEEB at postoperative 1, 2, or 3 months (P < 0.01). Interface opacity was higher in the nDSAEK group than the DSAEK group at all examination points, but the difference was statistically insignificant. At 3 months after surgery, the CEEB were negative for Na(+)/K(+)-ATPase staining. Staining with TUNEL showed apoptotic changes in some areas. During a 6-month observation, the CEEB showed a time-dependent thickening and loss of uniform thickness of cellular morphology. At 3 and 6 months post nDSAEK, extensions of the cellular processes into the donor graft stroma combined with intracellular vacuoles containing collagen-like materials were also found. CONCLUSIONS After non-Descemets stripping automated endothelial keratoplasty, the CEEB showed decreased density, loss of pump function, apoptosis and changed morphology. However, the interface opacity was not significantly greater compared with DSAEK eyes.