Comparison of flanged polypropylene scleral intraocular lens fixation with scleral sutured fixation.

OBJECTIVE: To compare the outcome of 2 intraocular lens (IOL) scleral fixation techniques: double-flanged polypropylene and Hoffman scleral pocket. METHODS: Retrospective case series of all patients who underwent IOL scleral fixation by either the flange (flange group) or Hoffman scleral pocket (Hoffman group) techniques at the Kaplan Medical Center and the Edith Wolfson Medical Center. RESULTS: A total of 140 patients were included (63 flange, 77 Hoffman). The final distance-corrected visual acuity was similar between the flange and Hoffman groups (0.42 ± 0.5 and 0.51 ± 0.5 logMAR, respectively; p = 0.23), but the spherical equivalent was less myopic in the flange group (-0.63 ± 2 and -2.3 ± 1.3 D, respectively; p = 0.003). In the flange group, there were more cases of elevated IOP (17.5% vs 5.2%; p = 0.02), corneal edema (11.1% vs 1.3%; p = 0.02), cystoid macular edema (15.9% vs 2.6%; p = 0.005), and IOL decentration (19% vs 7.8%; p = 0.07). The flange group had a higher rate of combined additional procedures during the fixation surgery (68.3% vs 32%; p < 0.001), but surgery duration was not prolonged (70 vs 77 minutes; p = 0.29). CONCLUSION: Comparison of scleral IOL fixations performed with the recently developed flange technique to the conventional Hoffman scleral pocket technique resulted in similar visual outcomes and less myopization. There were more complications in the newly adopted flange technique, which may be related to the higher rate of combined anterior vitrectomy and pars plana vitrectomy. The flange technique is effective, with a shorter learning curve and similar surgical time. Therefore, it can become a viable method for scleral IOL fixation in the absence of zonular support.

Implantation and Evaluation of Melanoma in the Murine Choroid via Optical Coherence Tomography.

Establishing experimental choroidal melanoma models is challenging in terms of the ability to induce tumors at the correct localization. In addition, difficulties in observing posterior choroidal melanoma in vivo limit tumor location and growth evaluation in real-time. The approach described here optimizes techniques for establishing choroidal melanoma in mice via a multi-step sub-choroidal B16LS9 cell injection procedure. To enable precision in injecting into the small dimensions of the mouse uvea, the complete procedure is performed under a microscope. First, a conjunctival peritomy is formed in the dorsal-temporal area of the eye. Then, a tract into the sub-choroidal space is created by inserting a needle through the exposed sclera. This is followed by the insertion of a blunt needle into the tract and the injection of melanoma cells into the choroid. Immediately after injection, noninvasive optical coherence tomography (OCT) imaging is utilized to determine tumor location and progress. Retinal detachment is evaluated as a predictor of tumor site and size. The presented method enables the reproducible induction of choroid-localized melanoma in mice and the live imaging of tumor growth evaluation. As such, it provides a valuable tool for studying intraocular tumors.

Excimer laser-assisted corneal epithelial pattern ablation for corneal cross-linking.

PURPOSE: To determine corneal cross-linking (CXL) efficacy and chromophore penetration after excimer laser-assisted patterned de-epithelialization. METHODS: Two-hundred-twenty porcine eyes were de-epithelialized ex vivo, either fully (mechanical; n = 88) or patterned (excimer laser; n = 132). Consecutively, corneas were impregnated with hypo- or hyperosmolar riboflavin (RF; n = 20, RF-D; n = 40, respectively) or water-soluble taurine (WST11; n = 40, and WST-D; n = 40, respectively), or kept unimpregnated (n = 80). Sixty corneas were subsequently irradiated, inducing CXL, with paired contralateral eyes serving as controls. Outcome measurements included strip extensiometry to assess CXL efficacy, and spectrophotometry and fluorescence microscopy to determine stromal chromophore penetration. RESULTS: All tested chromophores induced significant CXL (p < 0.001), ranging from 7.6% to 14.6%, with similar stiffening for all formulations (p = 0.60) and both de-epithelialization methods (p = 0.56). Light transmittance was significantly lower (p < 0.001) after full compared with patterned de-epithelialization. Stromal chromophore penetration was comparable between fully and patterned de-epithelialized samples, with full penetration in RD and RF-D samples and penetration depths measuring 591.7 ± 42.8 µm and 592.9 ± 63.5 µm for WST11 (p = 0.963) and 504.2 ± 43.2 µm and 488.8 ± 93.1 µm for WST-D (p = 0.669), respectively. CONCLUSIONS: Excimer laser-assisted patterned de-epithelialization allows for effective CXL. Stromal chromophore concentration is, however, reduced, which may have safety implications given the need for sufficient UVA attenuation in RF/UVA CXL. The different safety profile of near-infrared (NIR) may allow safe WST11/NIR CXL even with reduced stromal chromophore concentration values. In vivo studies are needed to evaluate the benefits and further assess safety of excimer laser-assisted patterned de-epithelialization for corneal CXL.

Implantation of an Artificial Endothelial Layer for Treatment of Chronic Corneal Edema.

PURPOSE: The purpose of this study was to describe a novel device that may serve as an alternative to Descemet membrane endothelial keratoplasty (DMEK) for the treatment of chronic corneal edema. METHODS: The EndoArt (EyeYon Medical, Israel) is a flexible, 50-µm thin artificial endothelial layer that matches the cornea's posterior curvature and functions as a fluid barrier at the posterior stroma, replacing the diseased endothelium. Similar to a DMEK approach, it is implanted into the anterior chamber, carefully positioned on the posterior stroma, and secured using an air-gas mixture. Two patients with chronic corneal edema resulting from endothelial decompensation underwent implantation of the new artificial lamella. RESULTS: In patient 1, the central corneal thickness (CCT) decreased from 730 µm preoperatively to 593 µm at 1 day postoperatively. In patient 2, the CCT decreased from 761 µm preoperatively to 487 µm at 1 day postoperatively. Both patients reported high satisfaction and an overall brighter visual quality. Although dislocation of the lamella occurred in both cases, the CCT was promptly restored after a repositioning procedure and remained stable at the 17-month follow-up (CCT of 526 and 457 µm for patients 1 and 2, respectively). In contrast to DMEK donor tissue, the artificial lamella is sufficiently robust to allow easy intraocular manipulation without the risk of damaging the implant. It is easily removable and does not require any immunosuppressive treatment because of its nonbiological nature. CONCLUSIONS: Implantation of the EndoArt led to rapid corneal deturgescence and CCT restoration, presenting a possible option for patients with chronic corneal edema.

In-vivo imaging for assessing tumor growth in mouse models of ocular melanoma.

Uveal melanoma (UM) and conjunctival melanoma (CM) are ocular malignancies that give rise to life-threatening metastases. Although local disease can often be treated successfully, it is often associated with significant vision impairment and treatments are often not effective against metastatic disease. Novel treatment modalities that preserve vision may enable elimination of small tumors and may prevent subsequent metastatic spread. Very few mouse models of metastatic CM and UM are available for research and for development of novel therapies. One of the challenges is to follow tumor growth in-vivo and to determine the right size for treatment, mainly of the posterior, choroidal melanoma. Hence, the purpose of this study was to establish a simple, noninvasive imaging tool that will simplify visualization and tumor follow-up in mouse models of CM and UM. Tumors were induced by inoculation of murine B16LS9 cells into the sub-conjunctival or the choroidal space of a C57BL/6 mouse eye under a surgical microscope. Five to ten days following injection, tumor size was assessed by Phoenix MicronIV™ image-guided Optical Coherence Tomography (OCT) imaging, which included a real-time camera view and OCT scan of the conjunctiva and the retina. In addition, tumor size was evaluated by ultrasound and histopathological examination of eye sections. Tumor growth was observed 5-9 days following sub-conjunctival or sub-retinal injection of seven-thousand or seventy-thousand cells, respectively. A clear tumor mass was detected at these regions using the MicronIV™ imaging system camera and OCT scans. Histology of eye sections confirmed the presence of tumor tissue. OCT allowed an accurate measurement of tumor size in the UM model and a qualitative assessment of tumor size in the CM model. Moreover, OCT enabled assessing the success rate of the choroidal tumor induction and importantly, predicted final tumor size already on the day of cell inoculation. In conclusion, by using a simple, non-invasive imaging tool, we were able to follow intraocular tumor growth of both CM and UM, and to define, already at the time of cell inoculation, a grading scale to evaluate tumor size. This tool may be utilized for evaluation of new mouse models for CM and UM, as well as for testing new therapies for these diseases.

Enzymatic Digestion of Porcine Corneas Cross-linked by Hypo- and Hyperosmolar Formulations of Riboflavin/ultraviolet A or WST11/Near-Infrared Light.

Purpose: To assess enzymatic digestion rate after Riboflavin (RF) and Water-Soluble-Taurine (WST11) based corneal cross-linking (CXL), with or without the addition of high molecular weight dextran (RF-D and WST-D). Methods: Eighty-eight paired porcine corneas were cross-linked by either RF (n = 11) or RF-D (n = 11) and ultraviolet light (UVA), or WST11 (n = 11) or WST-D (n = 11) and near-infrared (NIR) light, or used as paired control (n = 44). Corneal buttons of treated and paired control eyes were placed in a 0.3% collagenase solution. Time to full digestion and remaining dry sample weight after six hours were compared. Results: A strong treatment effect was seen with all four formulations, as all controls had been fully digested whilst all treated samples were still visible at the experiment's endpoint. After irradiation, central corneal thickness was significantly higher in samples treated with hypo-osmolar formulations, compared to dextran enriched formulations (P < 0.001). Dry sample weight after digestion was nonsignificantly different between corneas treated by the four different formulations (P = 0.102). Average dry sample weight was 1.68 ± 0.6 (n = 10), 2.19 ± 0.50 (n = 8), 1.48 ± 0.76 (n = 11), and 1.54 ± 0.60 (n = 9) mg, for RF, RF-D, WST11, and WST-D treated samples, respectively. Enzymatic resistance was similar for RF and WST based CXL (P = 0.61) and was not affected by the addition of dextran (P = 0.221). Conclusions: Both RF and WST11 based CXL significantly increases resistance to enzymatic digestion, with similar effect for hypo-osmolar and hyperosmolar (dextran enriched) formulations. Translational Relevance: Our findings indicate these formulations are interchangeable, paving the way for the development of novel PACK-CXL protocols for thin corneas and deep-seated infections.

Decreased Riboflavin Impregnation Time Does Not Increase the Risk for Endothelial Phototoxicity During Corneal Cross-Linking.

Purpose: To evaluate the riboflavin (RF) concentration and distribution in the corneal stroma and the risk for endothelial photodamage during corneal crosslinking (CXL) following 10- and 30-minute impregnation. Methods: De-epithelialized rabbit corneas were subjected to impregnation for 10 and 30 minutes with different RF formulations. Human corneal endothelial cells (HCECs) were subjected to different RF concentrations and ultraviolet A (UVA) dosages. Assays included fluorescence imaging, absorption spectroscopy of corneal buttons and anterior chamber humor, and cell viability staining. Results: After 10 and 30 minutes of impregnation, respectively, anterior chamber fluid showed an RF concentration of (1.6 ± 0.21)•10-4% and (5.4 ± 0.21)•10-4%, and trans-corneal absorption reported an average corneal RF concentration of 0.0266% and 0.0345%. This results in a decrease in endothelial RF concentration from 0.019% to 0.0056%, whereas endothelial UVA irradiance increases by 1.3-fold when changing from 30 to 10 minutes of impregnation. HCEC viability in cultures exposed to UVA illumination and RF concentrations as concluded for the endothelium after 10- and 30-minute impregnation was nonstatistically different at 51.0% ± 3.9 and 41.3 ± 5.0%, respectively. Conclusions: The risk for endothelial damage in CXL by RF/UVA treatment does not increase by shortened impregnation because the 30% increase in light intensity is accompanied by a 3.4-fold decrease of the RF concentration in the posterior stroma. This is substantiated by similar endothelial cell toxicity seen in vitro, which in fact appears to favor 10-minute impregnation. Translational Relevance: This study offers compelling arguments for (safely) shortening RF impregnation duration, reducing patients' burden and costly operation room time.

Repetitive magnetic stimulation protects corneal epithelium in a rabbit model of short-term exposure keratopathy.

PURPOSE: To investigate the effect of repetitive magnetic stimulation (RMS) on corneal epithelial permeability in a rabbit model of exposure keratopathy. METHODS: 61 female New Zealand White (NZW) rabbits were treated on one eye with repetitive magnetic stimulation (RMS) at a frequency of 20 Hz for 15 min. The other eye was untreated. Rabbit eyes were kept open for 2 h to induce acute corneal desiccation. The extent of fluorescein corneal staining was evaluated using EpiView software and the concentration of fluorescein in the anterior chamber was determined by a fluorometer. Safety was evaluated by electroretinogram, spectral domain optical coherence tomography (SD-OCT) and histopathology. Expression pattern of corneal cell markers was determined by immunofluorescence. RESULTS: A significant decrease in fluorescein concentration in the anterior chamber (54 ±â€¯8.4 ng/ml vs. 146.5 ±â€¯18.6 ng/ml, p = 0.000001) and in corneal surface fluorescein staining score (1.7 ±â€¯0.2 vs. 4.6 ±â€¯0.6, p = 0.00001) was obtained in RMS-treated eyes compared with control eyes, respectively. RMS treatment reduced by nearly 4 fold the percentage of corneal area with epithelial erosions by anterior segment SD-OCT. The therapeutic effect was maintained for at least 3 months. Increased expression of epithelial tight junction protein Zo-1 was observed in treated eyes. SD-OCT and histopathology analysis revealed no pathological changes in the treated or non-treated eyes. CONCLUSIONS: RMS treatment decreases epithelial corneal erosions in a rabbit model of exposure keratopathy, with no indication of pathological changes. RMS may present a novel treatment for protection of corneal epithelium from desiccation.

The effect of estrogen and progesterone on porcine corneal biomechanical properties.

PURPOSE: To determine the effect of the hormones estrogen and progesterone on the biomechanical properties of porcine corneas. METHODS: Thirty fresh porcine corneas were acquired from an abattoir. The corneas were equally divided into three groups. Groups were incubated for 1 week in Eusol-C solution containing supra-physiologic concentrations of estrogen, progesterone, or control (no added hormone). After incubation, the central corneal thickness (CCT) of each cornea was measured using an electronic caliper, and then the corneas were cut into strips. The strips were then clamped in the pneumatic jaws of a computer-controlled biomaterial tester (Instron 4502, USA) and stretched at a constant rate of 1 mm/min until tissue rupture while constantly recording the stress and strain of the tissue. Stress-strain curves were plotted and Young's modulus was calculated for each corneal strip. RESULTS: Average corneal thickness was 873.5 ± 143.1 µm for the control group, 928.0 ± 97.7 µm for the estrogen group, and 922.0 ± 116.7 µm for the progesterone group (data presented as mean ± SD). There was no statistically significant difference between the groups regarding the CCT (p = 0.89). The average Young's modulus was 17.00 ± 3.46 MPa for the control group, 16.95 ± 6.83 MPa for the progesterone group, and 12.33 ± 3.24 MPa for the estrogen group. The difference between the control and estrogen groups was statistically significant (p = 0.018) while the difference between the control and progesterone groups was not (p = 0.72). CONCLUSION: Estrogen has a relaxing effect on the porcine cornea, resulting in reduced stiffness of the tissue. Progesterone has no significant effect on the biomechanical properties of porcine corneas. Estrogen and progesterone do not significantly affect CCT.

Multimodal Assessment of Corneal Erosions Using Optical Coherence Tomography and Automated Grading of Fluorescein Staining in a Rabbit Dry Eye Model.

PURPOSE: To evaluate the potential use of anterior segment spectral domain optical coherence tomography (AS-SD-OCT) combined with an automated grading of fluorescein staining for assessment of corneal erosions in a rabbit short-term dry eye model. METHODS: Twenty-one New Zealand white rabbits were anesthetized and eyes were kept open for 140 minutes to induce acute corneal desiccation. Rectangular scans of the cornea were performed using Spectralis AS-SD-OCT. Total corneal thickness, corneal epithelial thickness, and the percentage of epithelial erosion area (PEEA) were evaluated. Corneas were stained with fluorescein and graded automatically using EpiView and semi-automatically using ImageJ. Spearman's rank-order correlations were calculated to compare the AS-SD-OCT PEEA and the two corneal staining scores. RESULTS: Eye desiccation resulted in corneal epithelium erosions that covered 0.67% to 14.2% of the central cornea (mean ± SD: 3.95% ± 3.2%) by AS-SD-OCT. The percentage of corneal area positively stained with fluorescein ranged from 0.24% to 38.01% (mean ± SD: 12.24% ± 9.7%) by using ImageJ, correlating with the AS-SD-OCT PEEA (Spearman's ρ, 0.574; P = 0.007). The EpiView score ranged from 0.5 to 10.17 and was better correlated with the AS-SD-OCT PEEA score (Spearman's ρ, 0.795; P = 0.000017). CONCLUSIONS: Our study suggests that multimodal analysis of AS-SD-OCT and grading of fluorescein staining using EpiView software may enable quantitative assessment of corneal epithelial erosions in a rabbit short-term dry eye model. TRANSLATIONAL RELEVANCE: This multimodal imaging analysis may be applied for evaluation of superficial punctate keratitis associated with dry eye.

Opacification of hydrophilic intraocular lenses associated with vitrectomy and injection of intraocular gas.

OBJECTIVE: To report 11 cases of intraocular lens (IOL) opacification after pars plana vitrectomy (PPV) involving intravitreal gas injection. METHODS AND ANALYSIS: Eleven cases of hydrophilic IOLs that opacified following PPV with intravitreal gas injection are described. Eight IOLs were explanted and analysed by light microscopy and scanning electron microscopy. Staining with alizarin red and von Kossa stains, as well as energy dispersive X-ray spectroscopy (EDX) were performed. Three IOLs were not explanted. The surgeons attached the clinical data. RESULTS: The IOLs were hydrophilic acrylic produced by six manufacturers. Six patients underwent primarily phacoemulsification with IOL implantation. PPV with intravitreal gas injection was performed 3 months-6 years afterwards. The other five patients underwent combined phacoemulsification with IOL implantation and PPV with intravitreal gas injection. IOL opacification was recorded 1 month -6 years after PPV. In eight patients, the IOLs were explanted 1 month-9 years after opacification was noticed. In three patients, the opacified IOL was not explanted. IOLs had opacified mainly anteriorly at the pupillary entrance or capsulorhexis opening. Light microscopy demonstrated granular surface deposits on the IOLs that stained positive for calcium by alizarin red and von Kossa stains. EDX analysis of the deposits detected calcium and phosphorus. CONCLUSIONS: Hydrophilic acrylic IOLs can opacify due to calcium deposition after PPV and intravitreal gas injection and may require IOL explantation. A hydrophobic IOL may be preferred when a simultaneous phacoemulsification and vitrectomy with intravitreal gas is performed.

Long-Term Biomechanical and Histologic Results of WST-D/NIR Corneal Stiffening in Rabbits, Up to 8 Months Follow-up.

Purpose: To determine the long-term safety and efficacy of WST-D/near-infrared (NIR) corneal stiffening. Methods: One eye of 23 New Zealand White rabbits was de-epithelialized mechanically followed by topical application of 2.5 mg/mL WST11, combined with dextran-500 (WST-D) for 20 minutes. Subsequently, samples were irradiated with a NIR (755 nm) laser at 10 mW/cm2 for 30 minutes. Untreated fellow eyes served as controls. One week (n = 4), 1 month (n = 6), 4 months (n = 9), or 8 months (n = 4) after treatment rabbits were euthanized. Corneal strips were cut in superior-inferior direction for extensiometry testing (1, 4, and 8 months), and histologic sections were prepared for evaluation of keratocyte distribution (1 week and 8 months). Results: Elastic modulus after treatment was significantly higher than in paired controls (16.0 ± 2.3 MPa versus 9.6 ± 3.6 MPa [P = 0.008], 18.1 ± 4.5 MPa versus 12.6 ± 2.3 MPa [P = 0.003], and 18.6 ± 3.6 MPa versus 14.2 ± 3.6 MPa [P = 0.010], at 1, 4, and 8 months, respectively). A significant decrease in keratocyte count at the anterior stroma was observed directly after treatment (1.5 ± 1.7 vs. 19.0 ± 4.1 [P = 0.002]). At 8 months keratocyte repopulation appeared completed, with similar distribution in treated and untreated corneas (15.9 ± 1.1 vs. 14.5 ± 2.5 [P = 0.562]). Corneal thickness was comparable between treated and untreated corneas at all time points. Conclusions: WST-D/NIR treatment resulted in significant and persistent long-term increase in corneal stiffness. Initial keratocyte apoptosis in the anterior stroma is followed by repopulation to normal level at 8 months after treatment. The safe nature of NIR light allows treatment of corneas of any thickness without endangering corneal endothelium or deeper ocular structures, potentially benefiting patients deemed unsuitable for riboflavin/UV-A cross-linking.

Corneal Stiffening by a Bacteriochlorophyll Derivative With Dextran and Near-Infrared Light: Effect of Shortening Irradiation Time up to 1 Minute.

PURPOSE: The aim of this study is to determine the effect of variation of the exposure time of near-infrared irradiation on corneal stiffening after a bacteriochlorophyll derivative (WST11) with dextran (WST-D) application. METHODS: One hundred four paired eyes of 3-month-old New Zealand White rabbits were included in this study. Fifty-two eyes (ex vivo n = 34, in vivo n = 18) were mechanically deepithelialized, treated topically with WST-D, and irradiated at 10 mW/cm using a diode laser at 755 nm for 1, 5, or 30 minutes. Untreated fellow eyes served as controls. Corneoscleral rings were removed immediately after treatment (ex vivo), or 1 month after treatment (in vivo). Corneal strips were cut and underwent biomechanical stress-strain measurements. RESULTS: Ex vivo, the mean tangent elastic modulus was significantly higher in the treatment groups than in the control groups for 1, 5, and 30 minutes of irradiation, respectively, 6.06 MPa, 95% confidence interval (CI, 4.5-7.6) versus 14.02 MPa, 95% CI (10.2-17.8), n = 11, 4.8 MPa, 95% CI (3.9-5.7) versus 15.03 MPa, 95% CI (12-18.1), n = 11, and 7.8 MPa, 95% CI (5.6-10.02) versus 16.2 MPa, 95% CI (13.6-18.9), n = 11; P < 0.001 for all comparisons. In vivo, the mean elastic moduli in the treatment groups were significantly higher for 5 and 30 minutes of irradiation but not for 1 minute of irradiation, respectively, 11.4 MPa, 95% CI (8.5-14.2), versus 17.1 MPa, 95% CI (14.5-19.7), n = 5; P < 0.001, and 9.4 MPa, 95% CI (5.1-13.8) versus 16 MPa, 95% CI (13.1-19), n = 5; P < 0.01, and 11.3 MPa, 95% CI (6-16.6) versus 12.2 MPa, 95% CI (7.5-16.8), n = 5; P = 0.7. CONCLUSIONS: WST-D/near-infrared treatment using shortened irradiation time (1 minute ex vivo and 5 minutes in vivo) results in significant corneal stiffening, and this might provide an alternative to the currently applied riboflavin/ultraviolet A cross-linking.

Digoxin derivatives with selectivity for the α2ß3 isoform of Na,K-ATPase potently reduce intraocular pressure.

The ciliary epithelium in the eye consists of pigmented epithelial cells that express the α1ß1 isoform of Na,K-ATPase and nonpigmented epithelial cells that express mainly the α2ß3 isoform. In principle, a Na,K-ATPase inhibitor with selectivity for α2ß3 that penetrates the cornea could effectively reduce intraocular pressure, with minimal systemic or local toxicity. We have recently synthesized perhydro-1,4-oxazepine derivatives of digoxin by NaIO4 oxidation of the third digitoxose and reductive amination with various R-NH2 substituents and identified derivatives with significant selectivity for human α2ß1 over α1ß1 (up to 7.5-fold). When applied topically, the most α2-selective derivatives effectively prevented or reversed pharmacologically raised intraocular pressure in rabbits. A recent structure of Na,K-ATPase, with bound digoxin, shows the third digitoxose approaching one residue in the ß1 subunit, Gln84, suggesting a role for ß in digoxin binding. Gln84 in ß1 is replaced by Val88 in ß3. Assuming that alkyl substituents might interact with ß3Val88, we synthesized perhydro-1,4-oxazepine derivatives of digoxin with diverse alkyl substituents. The methylcyclopropyl and cyclobutyl derivatives are strongly selective for α2ß3 over α1ß1 (22-33-fold respectively), as determined either with purified human isoform proteins or intact bovine nonpigmented epithelium cells. When applied topically on rabbit eyes, these derivatives potently reduce both pharmacologically raised and basal intraocular pressure. The cyclobutyl derivative is more efficient than Latanoprost, the most widely used glaucoma drug. Thus, the conclusion is that α2ß3-selective digoxin derivatives effectively penetrate the cornea and inhibit the Na,K-ATPase, hence reducing aqueous humor production. The new digoxin derivatives may have potential for glaucoma drug therapy.

Prediction of refractive outcomes with toric intraocular lens implantation.

PURPOSE: To evaluate and compare the accuracy of different methods to measure and predict postoperative astigmatism with toric intraocular lens (IOL) implantation. SETTING: Ein-Tal Ophthalmology Center, Tel-Aviv, Israel. DESIGN: Retrospective case series. METHODS: Postoperative corneal astigmatism was measured with 3 devices (IOLMaster 500; optical low-coherence reflectometry [OLCR]-based Lenstar LS 900; Atlas topographer) and compared with the manifest astigmatic refractive outcome in patients with toric IOLs. The error in the predicted residual astigmatism was calculated by vector analysis according to the measurement and calculation method used to predict the required toric IOL cylinder power. RESULTS: The centroid errors in predicted residual astigmatism were against the rule with the Alcon and Holladay toric calculators (0.53 to 0.56 diopter [D]), were lower with the Baylor nomogram (0.21 to 0.26 D), and were lowest for the Barrett toric calculator (0.01 to 0.16 D) (P <.001). The Barrett toric calculator had the lowest median absolute error in predicted residual astigmatism (0.35 to 0.54 D, all devices) compared with the Alcon and Holladay toric calculators with or without the Baylor nomogram (P <.021). The Barrett toric calculator and the OLCR device achieved the most accurate results; 75.0% and 97.1% of eyes were within ±0.50 D and ±0.75 D of the predicted residual astigmatism, respectively. CONCLUSION: Prediction of astigmatic outcomes with toric IOLs can be improved with appropriate measuring devices and methods to establish the required toric IOL power.

Low-dose pulsed intravenous cyclophosphamide for severe ocular cicatricial pemphigoid in elderly patients.

PURPOSE: Ocular cicatricial pemphigoid (OCP) is a relatively rare autoimmune disease affecting elderly patients and causing severe symptoms that may culminate in blindness. Treatment is based on immunosuppression, but optimal regimens have not been established. METHODS: A prospective unmasked case series of all patients with severe OCP who gave consent and completed treatment and ≥6 months of follow-up in the cornea and immunomodulation outpatient clinics of an academic hospital. Monthly pulses of intravenous cyclophosphamide (IVC; 500 mg) were administered with ondansetron and adjusted according to response. RESULTS: Over 14 years, 13 patients (median age 77 years) met inclusion criteria. All had bilateral OCP (2 eyes were previously blind), but extraocular involvement was rare (1/13). Three to 28 pulses were given, and the patients were followed up for a median of 32 (range, 6-167) months. Remission of inflammation in both eyes was achieved in 12 patients (92%). Vision improved in 5 of 13 patients, stabilized in another 5 (combined, 77%), and worsened in only 3 patients. One patient's condition flared up during treatment that responded to steroids and increasing IVC frequency. In 4 patients and 6 eyes (25%), cicatrization progressed (usually, Foster stages 1-3). Two late relapses occurred and responded to retreatment. IVC was generally well tolerated, although nausea led to modification in 2 patients. One patient developed candida keratitis. CONCLUSIONS: Compared with other treatment modalities, low-dose monthly pulse IVC is found to be a relatively safe, simple, and usually effective alternative immunosuppressive treatment in severe OCP.

Penetration of moxifloxacin through crosslinked corneas.

PURPOSE: To determine the ability of moxifloxacin to penetrate the rabbit eye after corneal collagen crosslinking (CXL) with riboflavin and ultraviolet-A light irradiation. SETTING: Harlan Biotech Israel, Rehovot, Israel. DESIGN: Experimental study. METHODS: One eye of 10 New Zealand white rabbits had CXL treatment. One month after treatment and 1 hour before an aqueous humor sample was obtained, 1 drop of 5 mg/mL moxifloxacin (Vigamox) was applied to both eyes of each rabbit every 15 minutes for a total of 4 drops. The aqueous humor samples were sent for high-performance liquid chromatography for antibiotic-concentration analysis. The eyes were enucleated and sent for histology analysis. RESULTS: Moxifloxacin levels were obtained and analyzed for all 20 eyes. The mean level of moxifloxacin was 2.26 µg/mL ± 0.89 (SD) (range 1.09 to 4.20 µg/mL) in the treated eyes and 2.43 ± 1.17 µg/mL (range 0.89 to 4.72 µg/mL) in the untreated eyes. The difference between the groups was not statistically significant. Of the 10 eye pairs, lower moxifloxacin aqueous humor concentrations were found in 6 treated eyes and 4 untreated eyes. CONCLUSION: Penetration of moxifloxacin into the anterior chamber of rabbits was not influenced by previous CXL treatment. FINANCIAL DISCLOSURES: No author has a financial or proprietary interest in any material or method mentioned.

Digoxin derivatives with enhanced selectivity for the α2 isoform of Na,K-ATPase: effects on intraocular pressure in rabbits.

In the ciliary epithelium of the eye, the pigmented cells express the α1ß1 isoform of Na,K-ATPase, whereas the non-pigmented cells express mainly the α2ß3 isoform of Na,K-ATPase. In principle, a Na,K-ATPase inhibitor with selectivity for α2 could effectively reduce intraocular pressure with only minimal local and systemic toxicity. Such an inhibitor could be applied topically provided it was sufficiently permeable via the cornea. Previous experiments with recombinant human α1ß1, α2ß1, and α3ß1 isoforms showed that the classical cardiac glycoside, digoxin, is partially α2-selective and also that the trisdigitoxose moiety is responsible for isoform selectivity. This led to a prediction that modification of the third digitoxose might increase α2 selectivity. A series of perhydro-1,4-oxazepine derivatives of digoxin have been synthesized by periodate oxidation and reductive amination using a variety of R-NH2 substituents. Several derivatives show enhanced selectivity for α2 over α1, close to 8-fold in the best case. Effects of topically applied cardiac glycosides on intraocular pressure in rabbits have been assessed by their ability to either prevent or reverse acute intraocular pressure increases induced by 4-aminopyridine or a selective agonist of the A3 adenosine receptor. Two relatively α2-selective digoxin derivatives efficiently normalize the ocular hypertension, by comparison with digoxin, digoxigenin, or ouabain. This observation is consistent with a major role of α2 in aqueous humor production and suggests that, potentially, α2-selective digoxin derivatives could be of interest as novel drugs for control of intraocular pressure.

Corneal collagen cross-linking for the treatment of progressive keratoconus: 3-year prospective outcome.

OBJECTIVE: To assess the long-term effects of treatment of progressive keratoconus with ultraviolet A-riboflavin collagen cross-linking (CXL). DESIGN: This was a prospective clinical study. PARTICIPANTS: Seventeen eyes of 17 patients with progressive keratoconus were treated with CXL. METHODS: Patients were examined preoperatively, at week 1, months 1, 3, 6, 9, 12, 24, and 36 after treatment. We assessed uncorrected visual acuity (UCVA) and best spectacle-corrected visual acuity (BSCVA), refraction, biomicroscopy and fundus appearance, intraocular pressure, endothelial cell density (ECD), corneal topography, minimal corneal thickness (MCT), macular optical coherence tomography, axial length, and corneal biomechanics with the ocular response analyzer. RESULTS: Comparing the 36-month time point results with pretreatment values, we found that UCVA and BSCVA were unchanged. Steepest meridian keratometry (D) and mean cylinder (D) did not show significant change compared with pretreatment values but showed a slight increase as compared with the 24-month time point (53.9 vs 51.7 vs 52.5, and 10.5 vs 8.1 vs 9.2 before, at 24 months, and at 36 months, respectively). Axial length (mm) showed an elongation trend throughout the follow-up period (24.56 vs 24.61 [p = 0.04] vs 24.71 [p = 0.05], before, at 24 months, and at 36 months, respectively). No significant change was observed in ECD, corneal hysteresis and corneal resistance factor, MCT, or foveal thickness. CONCLUSIONS: Three-year results after CXL show stable visual acuity, stable corneal thickness, and stable corneal biomechanical parameters. The decreasing trend in keratometry values that was observed during the first 2 years after CXL was no longer evident. Longer follow-up is needed to decide whether it is a first sign of loss of achieved stability and resumption of keratoconus progression.

Hydrophilic acrylic intraocular lens as a drug delivery system: influence of the presoaking time and comparison to intracameral injection.

PURPOSE: To evaluate the influence of different intraocular lens (IOL) presoaking times in an antibiotic solution and to compare the results with intracameral antibiotic injection alone. METHODS: Part A: 45 IOLs were soaked in gatifloxacin, moxifloxacin, or prednisolone acetate for 10 min, 24 h, and 1 week and then placed in a vial with a balanced salt solution. The solutions were sampled 12 and 24 h later. Part B: 90 eyes of 45 rabbits were divided into three groups. Group A received intracameral injection of moxifloxacin after lens removal and nonpresoaked IOL implantation. Groups B and C were implanted with IOLs that were presoaked for 15 min in moxifloxacin (group B) or gatifloxacin (group C), after lens removal with no intracameral antibiotic injections. Aqueous humor samples were taken 2, 4, 6, 8, and 10 h after surgery for high-performance liquid chromatography. RESULTS: Part A: In comparison with the 24-h group, the 10-min group showed release of about 30% of the antibiotics amount; the 1-week group showed a longer release time of the antibiotics and an increase of 27% for gatifloxacin and 43% for moxifloxacin. No prednisolone acetate was found. Part B: The moxifloxacin concentrations in the intracameral injection group were higher after surgery, but with faster antibiotic decrease in comparison with both presoaked IOL groups. CONCLUSION: Intracameral antibiotic injection showed a high antibiotic concentration for a short time. Presoaked IOLs showed slower decrease rates of the antibiotic level.