Comparison of central corneal thickness and anterior chamber depth measurements using three imaging technologies in normal eyes and after phakic intraocular lens implantation.

BACKGROUND: The repeatability and interchangeability of imaging devices measuring central corneal thickness (CCT) and anterior chamber depth (ACD) are important in the assessment of patients considering refractive surgery. The purpose of this study was to investigate the agreement of CCT and ACD measurements using three imaging technologies in healthy eyes and in eyes after phakic intraocular lens implantation (pIOL). METHODS: In this comparative study, CCT and ACD were measured using anterior segment optical coherence tomography (AS-OCT), Orbscan II, and Pentacam in 33 healthy volunteers (66 eyes) and 22 patients (42 eyes) after pIOL implantation. Intraobserver repeatability was evaluated for all three devices in the healthy volunteer group. RESULTS: Pairwise comparison of CCT measurements showed significant differences between all devices (P < 0.001), except for the AS-OCT and Orbscan II in the healthy volunteer group (P = 0.422) and the Orbscan II and Pentacam in the pIOL group (P = 0.214). ACD measurements demonstrated significant differences between all pairwise comparisons in both groups (P < or = 0.001). Intraobserver reliability was high for CCT and ACD measurements in the healthy volunteer group, with coefficients of variation ranging from 0.6% to 1.2% and 0.4% to 0.5% respectively. CONCLUSIONS: CCT and ACD measurements using AS-OCT, Orbscan II, and Pentacam demonstrated high intraobserver reliability. However, these devices should not be used interchangeably for measurements of CCT and ACD in healthy subject and patients after pIOL implantation.

Iris-fixated anterior chamber phakic intraocular lens for myopia moves posteriorly with mydriasis.

PURPOSE: To elucidate the physiological characteristics of eyes implanted with iris-fixated anterior chamber phakic intraocular lenses (pIOLs), which are increasingly being used for the correction of higher myopic and hyperopic refractive errors. METHODS: In a case series of 20 patients (39 eyes), the position of the pIOL to the natural lens and the cornea was evaluated under photopic (135 lux) and low mesopic (< 1 lux) circumstances with anterior segment optical coherence tomography. RESULTS: The distance between the pIOL and the natural lens decreased, and congruently, the distance from the pIOL to the corneal endothelium increased under low mesopic circumstances. CONCLUSIONS: The distance between the pIOL and the corneal endothelium increases when the pupil dilates under dark circumstances, contributing to the already excellent safety data available on pIOL implantation.

Case of late-onset corneal decompensation after iris-fixated phakic intraocular lens implantation.

A 48-year-old myopic patient with bilateral anterior chamber depth of 3.1 mm and endothelial cell density (ECD) of 2525 cells/mm(2) and 2638 cells/mm(2) preoperatively had bilateral implantation of an Artisan iris-fixated phakic intraocular lens (pIOL). Five years postoperatively, unilateral corneal stromal edema was seen in a circumscribed area overlying the temporal ridge of the pIOL in the right eye; the ECD was 1631 cells/mm(2) and the pachymetry, 586 microm. Explantation of the pIOL was refused by the patient. Seven years postoperatively, the ECD was 413 cells/mm(2) in the right eye and corneal decompensation occurred. The progressive unilateral endothelial loss was explained by excessive rubbing of the eyes because of chronic itching and an anterior shift of the pIOL over the 7 years as demonstrated by anterior optical coherence tomography.

Capacity and tolerance of a new device for ocular drug delivery.

A new method to increase the drug-capacity of the OphthaCoil, a flexible and tubular device for delivery of drugs to the tear film of the eye, was explored. Poly(2-hydroxyethyl methacrylate)- and poly(2-hydroxyethyl methacrylate-co-1-vinyl-2-pyrrolidone)-microspheres were prepared by suspension polymerization. The resultant particles were swollen in a highly concentrated solution of either the dye fluorescein sodium or the antibiotic chloramphenicol. The loaded particles were placed in the central cavity of the ocular device. In vitro release profiles showed a six-fold increase of the capacity for the dye fluorescein sodium, but not for the antibiotic chloramphenicol. Flexibility measurements revealed that by introducing microspheres in the central cavity of the device, flexibility did not decrease. Finally, a preliminary in vivo evaluation of the device (n=5) was done for a 2h-period to assess the tolerance of the device in the human eye. Ophthalmologic examinations and photographs of the eye indicated no signs of irritation. Volunteers reported that the presence of the device in the eye could be noticed, but no irritation was reported.

A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis.

PURPOSE: To determine the feasibility, safety, and effectiveness of an episcleral or deep scleral lamellar sustained release cyclosporine (CsA) device in a naturally occurring animal model of uveitis. METHODS: A two-compartment perfusion chamber was used to assess in vitro human and equine scleral permeability of fluorescein, dexamethasone-fluorescein, or CsA. A biodegradable, matrix-reservoir CsA implant was designed, and release rates of CsA were determined in vitro. Tissue CsA levels were measured in eyes with the implant. Horses with equine recurrent uveitis (ERU) received episcleral or deep scleral lamellar CsA implants and were monitored for up to 3 years. RESULTS: Dexamethasone-fluorescein and CsA penetrated the in vitro equine sclera poorly; however, low but detectable levels of CsA were detected intraocularly in vivo. The implant placed episclerally failed to control inflammatory episodes in ERU. CsA implants placed in the deep sclera adjacent to the suprachoroidal space resulted in high levels of CsA in most ocular tissues. In clinical equine patients with ERU, frequency of uveitic flare-ups was significantly decreased after implantation of a deep scleral lamellar CsA implant. CONCLUSIONS: Diffusion of CsA across the sclera from the episcleral space was not a feasible method of drug delivery to the equine eye. However, placing a deep scleral lamellar CsA implant adjacent to the suprachoroidal space was effective in achieving therapeutic ocular drug concentrations and controlling uveitis in horses with ERU.

Effective transscleral delivery of two retinal anti-angiogenic molecules: carboxyamido-triazole (CAI) and 2-methoxyestradiol (2ME2).

PURPOSE: To evaluate the human transscleral diffusion and intravitreal delivery of carboxyamido-triazole (CAI) and 2-Methoxyestradiol (2ME2). METHODS: The transscleral diffusion of two retinal antiangiogenic molecules, CAI and 2ME2, was measured in vitro to assess their potential transscleral delivery. Varying concentrations and different solvents of CAI and 2ME2 were placed in the upper compartment of a two-chamber acrylic perfusion apparatus, on the episcleral side of the sclera obtained from human donor eyes. Samples were taken from the lower compartment (uveal side) for up to 24 hours and measured by high performance liquid chromatography. RESULTS: All three solutions that contained CAI efficiently diffused through the sclera with permeability constants that ranged from 2.8 to 5.5 x 10 cm/s. The scleral permeability constant derived for 2ME2 was 9.96 x 10 cm/s. The permeability constants obtained for both CAI and 2ME2 are similar to each other as well as to permeability constants measured for other small molecules such as fluorescein and dexamethasone fluorescein. CONCLUSION: Both CAI and 2ME2 traverse the sclera efficiently. These data combined with the reported inhibition of posterior segment neovascularization observed with these two molecules demonstrates that CAI and 2ME2 are good candidate molecules to treat posterior segment neovascularization by local delivery.

The influence of intraocular pressure on the transscleral diffusion of high-molecular-weight compounds.

PURPOSE: To evaluate the effects of intraocular pressure on the permeability of the human sclera to high-molecular-weight compounds. METHODS: Human transscleral permeability to FITC-albumin (70 kDa) and 70-kDa and 150-kDa FITC-dextran was determined at transscleral pressures from 0 to 60 mm Hg. For each compound at each pressure, six to eight experiments were performed. Scleral sections were mounted in a two-compartment perfusion chamber. Temperature was maintained at 37 degrees C. Fractions of choroidal perfusate were collected, and fluorescence was measured with a spectrofluorometer. From these data, scleral permeability K(trans) (in centimeters per second) was calculated. RESULTS: Permeability to FITC-albumin was decreased by approximately one half when pressure was elevated from 0 to 30 mm Hg (P < 0.05). No significant differences in permeability to 70-kDa FITC-dextran were observed at pressures from 0 to 60 mm Hg. Permeability to 150-kDa FITC-dextran decreased by a little more than one half when transscleral pressure was raised from 0 to 15 mm Hg and was approximately 10 times lower at 60 mm Hg than at 0 mm Hg (P < 0.01). CONCLUSIONS: Human sclera was permeable to compounds with a molecular weight of up to 150 kDa at transscleral pressures ranging from 0 to 60 mm Hg. Transscleral diffusion was relatively unaffected by the pressure gradient, although for 150-kDa FITC-dextran at 60 mm Hg a 10-fold decrease was observed compared with that at 0 mm Hg. These experiments suggest that high-molecular-weight compounds (e.g., immunoglobulins and oligonucleotides) could be effectively delivered transsclerally to the intraocular tissues under circumstances of physiological or elevated intraocular pressure.

In vitro sustained human transscleral drug delivery of fluorescein-labeled dexamethasone and methotrexate with fibrin sealant.

PURPOSE: To study the use of fibrin sealant as a drug delivery system for the sustained transscleral delivery of dexamethasone and methotrexate. METHODS: Scleral sections excised from moist-chamber-stored human globes were mounted in a perfusion chamber. Dexamethasone-fluorescein or methotrexate-fluorescein in either fibrin sealant or balanced salt solution (BSS) was applied to the episcleral surface. BSS was perfused to the choroidal side, fluorescence was measured in perfusate fractions, and an apparent scleral permeability P(A) was calculated for each solute-vehicle combination. RESULTS: P(A) for both compounds was significantly lower with fibrin sealant delivery compared to delivery in BSS (p < 0.001). However, the fibrin sealant vehicle provided a more sustained release of both drugs through 24 hr. CONCLUSIONS: Incorporating dexamethasone and methotrexate into a fibrin sealant provided a more gradual drug delivery and a more uniform delivery compared to dissolving these drugs in BSS. Fibrin sealant could be useful for transscleral delivery for posterior segment disease.

In vitro human scleral permeability of fluorescein, dexamethasone-fluorescein, methotrexate-fluorescein and rhodamine 6G and the use of a coated coil as a new drug delivery system.

PURPOSE: To determine the in vitro human scleral permeability of several dyes and drugdye combinations with varying molecular weights (MW) and lipid solubilities (fluorescein, dexamethasone-fluorescein, methotrexate-fluorescein, and rhodamine). Coils coated with rhodamine were also evaluated for scleral permeability and sustained release. METHODS: Scleral sections excised from moist chamber stored human globes were mounted in a 2-compartment perfusion chamber. A small depot of drug/dye (100 microl of 10(-4) M fluorescein, dexamethasone-fluorescein, methotrexate-fluorescein or rhodamine) or a coated coil in 100 microl of BSS was added to the episcleral surface while perfusing BSS to the choroidal side. The perfusate was collected and measured for fluorescence. Permeability was calculated as Ktrans from the flux measurements. RESULTS: Ktrans values (cm/sec, mean +/- SE) for the studied dyes and drug-dye combinations were 5.21 +/- 0.71 x 10(-6) for fluorescein, 1.64 +/- 0.17 x 10(-6) for dexamethasone-fluorescein, 3.36 +/- 0.62 x 10(-6) for methotrexate-fluorescein, 1.86 +/- 0.39 x 10(-6) for rhodamine and 2.18 +/- 0.23 x 10(-6) for the rhodamine from the coils. We found a significant difference between the permeability of the sclera to fluorescein and dexamethasone-fluorescein (P < 0.001), methotrexate-fluorescein (P < 0.05) and rhodamine (P < 0.001). Steady state flux was observed from the rhodamine coil. CONCLUSION: The rank order of scleral permeability to the studied dyes is as follows: fluorescein > methotrexate-fluorescein > rhodamine coil > rhodamine 6G > dexamethasone-fluorescein. Differences in scleral permeability are related to MW and lipid solubility. Prolonged transscleral diffusion of rhodamine delivered by solution and by coil are similar.