Delmar Caldwell, MD, Chairman


Selected Publications

1. Heier J, Cheetham JK, Degryse R, Dirks,M.S.; Caldwell,D.R.; Silverstone,D.E. Ketorolac tromethamine 0.5% ophthalmic solution in the treatment of moderate to severe ocular inflammation after cataract surgery: a randomized, vehicle-controlled clinical trial. American Journal of Ophthalmology. 1999;127:253-9.

PURPOSE: To investigate the efficacy and safety of ketorolac tromethamine 0.5% ophthalmic solution (Acular; Allergan, Inc, Irvine, California) in the treatment of moderate to severe anterior segment inflammation developing after unilateral cataract surgery with intraocular lens implantation. METHODS: Only patients who exhibited moderate or greater levels of cells and flare 1 day after surgery were included in this multicenter, double-masked, randomly assigned, parallel-group study. Topical ketorolac or vehicle solution (Allergan, Inc) was administered to the treated eye four times daily, starting the day after surgery and continuing for 14 days. RESULTS: Ketorolac was significantly more effective than the vehicle solution in reducing anterior chamber cells (P < or = .030) and flare (P < or = .025), conjunctival erythema (P < or = .046), ciliary flush (P < or = .006), tearing (P < or = .012), photophobia (P < or = .014), and pain (P < or = .049). Half as many patients from the ketorolac group (14/51) were discontinued from the study for lack of efficacy, compared with the vehicle group (28/51; P = .005). There was no significant difference between ketorolac and the vehicle solution in changes in visual acuity, intraocular pressure, biomicroscopic or ophthalmoscopic variables, or adverse events. CONCLUSIONS: Ketorolac tromethamine 0.5% ophthalmic solution is safe and provides substantial anti-inflammatory activity in the treatment of moderate to severe anterior segment inflammation developing after cataract surgery and intraocular lens implantation.

2. Blake DA, Yu H, Young DL, Caldwell DR. Matrix stimulates the proliferation of human corneal endothelial cells in culture. Investigative Ophthalmology & Visual Science. 1997;38:1119-29.

PURPOSE: Extracellular matrices were tested for their ability to support the adhesion and proliferation of human corneal endothelial cells. METHODS:Human corneal endothelial cells were plated onto tissue culture dishes coated with purified fibronectin or a matrix elaborated by cultured bovine corneal endothelial cells. The presence of human cells in the cultures was confirmed by karyotyping. Cell size at increasing passage number was analyzed, and cellular response to growth factors was assessed using a 96-well microtiter plate assay. RESULTS: When tissue culture dishes were coated with fibronectin, the cells attached to the dish but grew slowly. Human corneal endothelial cells plated onto the matrices elaborated by bovine corneal endothelial cells attached to the culture dish and grew to fill the flask. At confluence, the cells had a hexagonal morphology similar to that seen in vivo. Karyotype analysis showed that the cells were of human and not bovine origin. The time required for senescence in culture was dependent on the age of the donor cornea. The bovine matrices enhanced the proliferative response of human corneal endothelial cell cultures to endothelial cell growth supplement and keratinocyte growth factor. Epidermal growth factor and hepatocyte growth factor stimulated human cell proliferation in a dose-dependent fashion, regardless of the substratum on which the cells were plated. CONCLUSIONS: The use of substratum elaborated by bovine corneal endothelial cells has proved useful in the preparation of human endothelial cell cultures from juvenile and adult donors. The method has been used to establish cultures from more than 50 donors from age 1 day to 76 years.

3. Caldwell DR. The soft keratoprosthesis. Transactions of the American Ophthalmological Society. 1997;95:751-802.

PURPOSE: The purpose of this work was to develop a keratoprosthesis which utilizes a biocolonizable skirt attached to a soft, elastomeric optic for world-wide application. METHODS: Over a period of 20 years, using in vivo animal implantation studies, a series of experiments was conducted testing materials for biocompatibility and durability which resulted in the development of an improved design. A new surgical technique was developed, using porous, biocolonizable haptics embedded within the sclera and combined with the established techniques of resection of Descemet's membrane and a conjunctival flap. RESULTS: Animal implantation studies indicated that 6 haptics, equidistantly placed, was the optimal shape. Two clinical trials resulted in the selection of an aliphatic polyether-based urethane for the optic and 60 mu pore polytetrafluoroethylene for the porous ingrowth material. Heated, pressurized injection moulding proved to be the optimal bonding method between the skirt and the optic. Sclerally embedded haptics achieved excellent integration with the tissue. CONCLUSIONS: This keratoprosthesis is a significant improvement over previous models with a rigid optic in that: 1. The porous ingrowth haptic is sclerally anchored, preventing extrusion. 2. It has a soft elastomeric optic which more successfully defuses the shearing forces of the keratoprosthesis/tissue interface secondary to blinking. 3. The optic is less massive and of greater circumference at the optic/tissue interface, thereby imparting less energy per area with a given movement. 4. The optic does not project posteriorly thereby decreasing anterior chamber irritation and reducing the possibility of glaucoma, uveitis, endophthalmitis, and retinal detachment. 5. This keratoprosthesis allows a normal field of view for the patient and an effective funduscopic view for the surgeon. 6. The large optical diameter eliminates problems with decentralization of the image. 7. It has a significantly better cosmetic appearance.

4. Hyndiuk RA, Eiferman RA, Caldwell DR, et al. Comparison of ciprofloxacin ophthalmic solution 0.3% to fortified tobramycin-cefazolin in treating bacterial corneal ulcers. Ciprofloxacin Bacterial Keratitis Study Group. Ophthalmology. 1996;103:1854-62.

PURPOSE: The purpose of the study is to compare the clinical efficacy and safety of ciprofloxacin ophthalmic solution 0.3% (Ciloxan) with a standard therapy regimen (fortified tobramycin, 1.3%-cefazolin, 5.0%) for treating bacterial corneal ulcers. METHODS: This randomized, parallel group, double-masked, multicenter study was conducted in 324 patients at 28 centers in the United States, Europe, and India. Patients were randomized into 2 treatment groups: 160 to ciprofloxacin and 164 to fortified tobramycin-cefazolin. Positive microbiologic cultures were obtained in 188 (58%) of 324 patients. Of these, 176 patients met protocol criteria and were evaluated for treatment efficacy: 82 in the ciprofloxacin group and 94 in the standard therapy group. The dosing schedule for both treatment groups was 1 to 2 drops of the first study medication (ciprofloxacin or fortified tobramycin) every 30 minutes for 6 hours, then hourly for the remainder of day 1; 1 to 2 drops every hour on days 2 and 3; 1 to 2 drops every 2 hours on days 4 and 5, followed by 1 to 2 drops every 4 hours on days 6 to 14. The second medication (ciprofloxacin or cefazolin) was instilled 5 to 15 minutes after the first drug, following the same dosing frequency. Physician's judgment of clinical success, cure rate, changes in ocular sings, and symptoms and the rate of treatment failures were the primary efficacy criteria. RESULTS: Topical ciprofloxacin monotherapy is equivalent clinically and statistically to the standard therapy regimen of fortified antibiotics. No statistically significant treatment differences were found between ciprofloxacin (91.5%) and standard therapy (86.2%) in terms of overall clinical efficacy (P = 0.34). Similarly, no differences were noted in resolution of the clinical signs and symptoms (P > 0.08) or the time to cure (P = 0.55). The incidence of treatment failures was less in the ciprofloxacin group (8.5%) compared with the standard therapy group (13.8%). Significantly fewer patients treated with ciprofloxacin reported discomfort than did patients treated with the standard therapy regimen (P = 0.01). CONCLUSION: Ciprofloxacin ophthalmic solution 0.3% monotherapy is equivalent clinically and statistically to standard therapy (fortified tobramycin-cefazolin) for the treatment of bacterial corneal ulcers and produces significantly less discomfort.

5. Wilhelmus KR, Hyndiuk RA, Caldwell DR, Abshire RL, Folkens AT, Godio LB. 0.3% ciprofloxacin ophthalmic ointment in the treatment of bacterial keratitis. The Ciprofloxacin Ointment/Bacterial Keratitis Study Group. Archives of Ophthalmology. 1993;111:1210-8.

OBJECTIVE: To determine the efficacy and safety of topical 0.3% ciprofloxacin hydrochloride ophthalmic ointment in the treatment of bacterial keratitis. DESIGN: Prospective case series with a nonrandomized comparison of culture-positive, evaluable cases (ciprofloxacin ointment group) with culture-positive, concurrent patients (nonenrolled group) treated with conventional therapy. SETTING: Multicenter clinical study. PATIENTS: After informed consent was obtained, 253 eligible patients underwent corneal scrapings and received topical ciprofloxacin ointment; 145 (57%) had positive cultures and completed the follow-up schedule. Forty (70%) of 57 apparently eligible patients had culture-positive bacterial keratitis but were not enrolled in the ciprofloxacin ointment study during the same period. INTERVENTION: Ciprofloxacin ophthalmic ointment instilled every 1 to 2 hours for 2 days, then every 4 hours for 12 days. MAIN OUTCOME MEASURES: Clinical evaluation of signs at 1, 3, 7, and 14 days of treatment and the overall condition classified as clinical success (cured or improved) or failure (unchanged or worse) during and after therapy. RESULTS: Clinical success with the initial treatment occurred in 135 patients (93%) in the ciprofloxacin ointment group and in 28 patients (70%) in the nonenrolled group. Of the 10 ciprofloxacin clinical failures, seven were staphylococcal; two, pneumococcal; and one, polybacterial. The 90% minimum inhibitory concentration of ciprofloxacin was 3 mg/L or less for corneal bacterial isolates. No serious adverse event attributable to ciprofloxacin ointment occurred, although 32 (13%) of 253 patients developed a transient white crystalline corneal precipitate shown with liquid chromatography in two cases to be ciprofloxacin. CONCLUSION: Ciprofloxacin ophthalmic ointment is an effective and safe topical antimicrobial agent for the treatment of bacterial keratitis caused by susceptible microorganisms.

6. Caldwell DR, Verin P, Hartwich-Young R, Meyer SM, Drake, MM. Efficacy and safety of lodoxamide 0.1% vs cromolyn sodium 4% in patients with vernal keratoconjunctivitis. American Journal of Ophthalmology. 1992;113:632-7.

A multicenter, double-masked, parallel-group clinical study compared the efficacy and safety of lodoxamide 0.1% ophthalmic solution and cromolyn sodium 4% ophthalmic solution in 120 patients with vernal keratoconjunctivitis. On various follow-up visits, the clinical efficacy of lodoxamide 0.1% was statistically superior to cromolyn sodium 4% in alleviating four of the primary symptoms (itching, tearing, foreign-body sensation, and discomfort) and five of the primary signs (Trantas' dots, palpebral conjunctival changes, bulbar conjunctival hyperemia, erythema/swelling of the eyelids and periorbital tissues, and epithelial disease). At no time during the study was cromolyn sodium 4% statistically superior to lodoxamide 0.1% in demonstrating improvements in clinical signs and symptoms of vernal keratoconjunctivitis. The physician's clinical judgment of patients' response to treatment showed lodoxamide 0.1% effected a greater and earlier improvement than cromolyn sodium 4%. Both drugs were safe for topical ophthalmic use when used four times daily for up to 28 days.

7. Caldwell DR, Miller DG. Goniotomy technique for removal of anterior chamber intraocular lenses. Ophthalmic Surgery. 1991;22:160-1.

Removal of an anterior chamber intraocular lens is often impeded by formation of peripheral anterior synechiae around one or more of the lens haptics. We describe a method of lysing adhesions under direct visualization through a contact gonioprism lens. This method is relatively atraumatic to vital anterior-chamber-angle structures.


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