Biomedical subjects
Publications and source records attributed to M F Refojo.
The water evaporation rate from the tear film of eyes with anterior surface pathology (corneal and/or conjunctival scars, meibomitis) was tested by means of the "Rolando-Refojo tear evaporimeter', which allows noninvasive and reproducible test conditions. These eyes show a statistically significant increase in tear evaporation rate compared to normal eyes. The clinical implications of this finding are discussed.
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The morphologic effect of hyperosmolarity, equivalent to that seen in the tear film of patients with keratoconjunctivitis sicca (KCS), on rabbit corneal epithelium in vitro and in vivo was studied. In the in vitro studies, corneal epithelium was grown in explant cultures. Control tissue was cultured in a 307 mOsm/L medium. Epithelium cultured in the 333, 361 and 363 mOsm/L media showed decreased intercellular connections, blunting and loss of microplicae, disruptions in cell membranes and cellular swelling with decreased cytoplasmic density. In in vivo studies, corneas bathed in balanced salt solutions (BSS) concentrated to 330, 360, or 407 mOsm/L showed increased cell desquamation, and the cell changes observed at similar osmolarities in the in vitro studies. The tear film osmolarities observed in KCS are sufficient to cause the corneal epithelial changes seen in patients with this disease.
MAI, a new hydrophilic implant designed by Refojo for scleral buckling, is soft and elastic (thus preventing erosion) and offers versatility in interconvertible degrees of softness. MAI has no dead spaces. Its ability to absorb and gradually release antibiotics and to stimulate the production of a fibrous capsule around the implant increases safety and minimizes morbidity associated with the scleral buckling operation. This review summarizes the works published to date on MAI.
The siloxanyl alkyl methacrylate copolymers with methyl methacrylate and other components including hydrophilic monomers and crosslinking agents are used to make siloxane methacrylate oxygen-permeable rigid contact lenses. These copolymers contain the element silicon as siloxane bonds in side branches of the main polymer chain, which is made of carbon-to-carbon bonds. The siloxane bonds are the main contributing factor to the oxygen permeability of these materials. Because silicone is not a component of these contact lenses, it is not appropriate to refer to them as silicone methacrylate contact lenses. This paper analyzes data from three fundamental patents and gives the oxygen permeability coefficients of three types of siloxanyl alkyl methacrylate copolymers. In one type the siloxanyl component contains two silicon atoms, in the second type it contains three silicon atoms, and in the third type it contains four silicon atoms. A general relationship, expressed by a power function, is developed between the oxygen permeability coefficients of siloxanyl alkyl methacrylate copolymers and dimethylsilicone rubber and their percent disiloxane or silicon content.
The terms dry eye and keratoconjunctivitis sicca (KCS) imply a condition of highly reduced or absent tear film that often is not clinically demonstrable despite the presence of other signs and symptoms. In 52 patients with KCS symptoms, either with or without tear volume reduction as measured by Schirmer's basic secretion test, we found a statistically significant increase in water evaporation rate from the tear film when compared with normal subjects. Such an increased evaporation rate might account for the tear hypertonicity known to be associated with KCS and postulated to be responsible for ocular surface damage. Thus, we propose to identify this group of paradoxically wet "dry eyes" as a "syndrome of increased tear evaporation", which better describes the pathogenesis of the ocular condition.
The rate of water evaporation from the tear film depends on the conditions under which it is determined. If measured in a controlled and easily reproducible setting, tear evaporation rate could serve as a useful diagnostic and research tool. We have developed a tear evaporimeter that provides a non-invasive method for evaluating water evaporation rate in eyes with normal or pathologic tear films. The subject is fitted with a pair of swimmer's goggles modified so that the air over the test eye is conditioned to a desired baseline of relative humidity (29.5%) and temperature (23 +/- 1 degree C). To eliminate other sources of water, the lids and skin under the goggles are covered with petroleum jelly. The subject is asked to keep his/her eye open and to avoid blinking during the 1-min test. The increase in relative humidity due to water evaporation from the tears is then determined. The surface area of the eye exposed to evaporation is calculated from the lid aperture. We measured the water evaporation rate in 52 normal eyes (average = 4.07 X 10(-7) +/- 0.40 X 10(-7) g/cm2/sec) and compared the results with values obtained in 52 eyes with various tear-film abnormalities (average = 8.17 X 10(-7) +/- 2.65 X 10(-7) g/cm2/sec). The difference between the two groups is statistically significant (P less than 0.01). In normal eyes, after the instillation of one drop of 0.5% proparacaine, the increase in evaporation rate was statistically significant.
Sustained release of carmustine (1,3-bis[2-chloroethyl]-1-nitrosourea, or BCNU) via an episcleral implanted silicone device was used to treat Greene hamster melanoma implanted in the anterior chamber of rabbit eyes. Group 1 animals received carmustine intravenously; group 2 received the drug by local sustained release via an episcleral implanted silicone device; group 3 received the drug by both local sustained release and intravenous injection (a total dosage more than twice that in group 1); and group 4 was not treated. The effectiveness of the various administration routes was compared by clinical observation of tumour size and systemic and local toxic reactions, and by histopathological examination. Carmustine delayed the growth of Greene melanoma in all 3 treated groups, but was most effective when a lower dose of the drug administered intravenously was combined with an additional higher dose administered by local sustained release. Local side effects included corneal clouding and conjunctival oedema and congestion at the early stage of local drug delivery via the episcleral implanted device.
The release rates of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), an anticancer drug, from various kinds of silicone and silicone-nylon implantable and refillable devices were investigated in vitro. The devices were made with different surface areas and wall thicknesses. The relation of the release rate at steady state to the surface area and the relation of the release rate per unit surface area to the wall thickness were determined. The relationship among the release rate, the surface area, and the wall thickness was analyzed using the multiple regression method, and is represented on a three-dimensional graph. The multiple regression equation predicts the release rate from the surface area and the wall thickness; the release rate can also be read from a nomogram that is presented.
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The oxygen transmissibility and hydration of new and used CSI, Hydrocurve II, and Hydromarc hydrogel contact lenses was determined at 37 degrees C. coatings that accumulated on used lenses were observed against a bright light and were graded in four classes from mild to severe. Some coated lenses had a statistically significant increase, and some a decrease in oxygen transmissibility compared with uncoated lenses. These differences are clinically unimportant, however. Although there seems to be a trend toward increased hydration and oxygen transmissibility with increased lens coating, statistically these relationships were found not to be linear. Failure of contact lenses after long-term wear must be due to causes other than a decrease in their oxygen transmissibility.
1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU), an anticancer drug, was assayed in the aqueous and vitreous of rabbits after intravenous injection, subconjunctival injection, and topical application. Pharmacokinetic parameters were calculated from the time-course curves. The penetration into aqueous and vitreous across the blood-aqueous barrier and the blood-retinal barrier after intravenous injection was related to the anatomic dimensions of the eye (the volume of tissue involved and the surface area through which BCNU diffuses). To evaluate the three routes of administration, the area under the time-course curve was calculated from the simulated time-course curve. The results suggest that topical application of BCNU is the best and subconjunctival injection the second best route for treating an iris tumor, and that intravenous injection is the best route for choroidal and retinal tumors.
The physiochemical properties of a hydrogel used as a scleral buckling implant for retinal detachment surgery are described. The new material was prepared by simultaneous polymerization and crosslinking of 2-hydroxyethyl acrylate with methyl acrylate and ethylene diacrylate, in the presence of an inert diluent, ethylene glycol. At equilibrium swelling, the hydrogen absorbed 17% water and had a durometer hardness (DH) of 15 (Shore Durometer A-2). A unique property of this material was its swelling hysteresis; when the gel swollen in 70% ethanol was placed in water, it retained a high level of hydration (75% water) and softness (DH 8), and most of its elasticity and strength as well. Then the swelling decreased very slowly so that the implant reached its ultimate size at equilibrium swelling in ca. 1 year. This property is especially useful in the scleral buckling procedure, in which a soft implant indents the sclera over the detached retina until reattachment is achieved. In addition to this advantage, this hydrogel is more elastic and stronger than available hydrogels of similar softness.
A new hydrophilic acrylate implant developed for scleral buckling was used in 51 patients: as an accessory meridional piece under a solid silicone buckle in 25 and as a main buckling element in 26 (intrasclerally in 15 and episclerally in 11). Clinical observations six to 18 months after implantation showed the implants to be well tolerated in all cases. There was no infection, rejection, extrusion of the implant, or erosion of the eye coats. In two patients who had reoperations, smooth fibrous tissue encapsulating the implant including the scleral bed was present. Our observations indicate that this new material has all the characteristics of an ideal implant for scleral buckling.
We evaluated the tolerance of ocular tissues to topical application of the anticancer agent 1,3 bis(2-chloroethyl)-1-nitrosourea (carmustine, BCNU) in eight normal rabbit eyes. Early changes in the anterior ocular structures, including moderate to severe chemosis, lid swelling, and superficial punctate keratitis with epithelial defect and corneal edema, occurred within the first 36 hours. These changes subsided gradually following administration of Cortisporin ointment (polymyxin B-bacitracin-neomycin-hydrocortisone) in the eyes that received 1.0 mg of BCNU per day. In one of the two eyes given the 3.0-mg dose, corneal clouding with interstitial vascularization was still present 40 days after drug administration, despite Cortisporin treatment.
Greene melanoma was transplanted into the anterior chamber of rabbit eyes. These animal models were divided into four groups. Group 1 received carmustine (1,3 bis [2-chloroethyl]-1-nitrosourea) intravenously. Group 2 received the drug by sub-Tenon-retrobulbar (periocular) injection. Group 3 received both periocular and intravenous administration; the combined dose was the same as that in group 1. Group 4 served as untreated control. The effectiveness of the various administration routes was compared by clinical observation of the size of the tumor growing in the eye, weight of the enucleated eyes, and histopathologic examination. Administration of carmustine delayed the growth of Greene melanoma in rabbit eye of all three treated groups, but effectiveness of treatment was considerably enhanced by combining periocular and intravenous administration of a lower dose of carmustine.
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