Concurrent cisplatin, infusional fluorouracil, and conventionally fractionated radiation therapy in head and neck cancer: dose-limiting mucosal toxicity.

After a preliminary dose-finding study involving 12 patients with advanced or locally recurrent head and neck cancer, 27 patients were treated on a phase II protocol, using fluorouracil 350 mg/m2/d by continuous intravenous (IV) infusion over 5 days, followed on the sixth day by a 2-hour IV infusion of cisplatin 50 mg/m2, administered during the first and fourth weeks of radiation therapy to total doses between 60 and 64 Gy, using 2 Gy daily fractions. Eight of these 27 patients had American Joint Committee on Cancer Staging (AJCC) stage III disease, and 12 had stage IV disease. Four had recurrent disease after surgery. Three-year follow-up is now available. Twenty-one (77.8%) remitted completely following treatment, and 11 remain free of local and regional relapse at 3 years. Four have developed systemic metastases. Following successful salvage treatment in two cases, estimated determinate survival at 3 years is 64%. Acute toxicity was manageable with this regime. Eleven instances of grade 3 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) mucositis were observed, which caused interruptions to radiotherapy in only four cases. No late sequelae have so far been recorded. It is concluded that the protocol described is tolerable but probably did not cause a greater number of locoregional "cures" than would have been expected following conventional radiotherapy alone in this group of patients. The use of infusional fluorouracil with concurrent conventionally fractionated radiation therapy and cisplatin infusion results in mucositis that limits the dose of fluorouracil to levels that are probably subtherapeutic.

Two- versus 24-hour infusion of cisplatin: pharmacokinetic considerations.

The disposition of unchanged cisplatin was compared after two- and 24-hour intravenous (IV) infusion to eight patients with germ cell cancer (dose, 100 mg/m2), 14 patients with head and neck cancer (dose, seven patients 50 mg/m2; seven patients, 100 mg/m2). Patients were randomized to receive either a two- or 24-hour infusion in the first course of treatment and the reverse in the second course. Cisplatin renal clearance, total clearance, and the percentage of the dose excreted unchanged in urine were significantly lower with the longer infusion. Total clearance was 345 +/- 97.0 mL/min/m2 after the two-hour infusion and 268 +/- 70.7 mL/min/m2 after the 24-hour infusion (P less than .0001). Renal clearance was 79.1 +/- 35.3 mL/min/m2 and 34.1 +/- 14.9 mL/min/m2 (P less than .0001). The percentage of the dose excreted unchanged in urine was 22.9 +/- 6.5% and 12.8 +/- 4.0%, respectively (P less than .0001). The ratio of cisplatin renal clearance to creatinine clearance was 1.95 +/- .96 after the two-hour infusion and .90 +/- .40 after the 24-hour infusion (P less than .001). There was only a poor relationship between cisplatin renal clearance and creatinine clearance after a two-hour infusion (r2 = .05, P greater than .1) or 24-hour infusion (r2 = .18, P greater than .05). The severity of emesis was graded on a four-point scale and was significantly less with the 24-hour infusion than with the two-hour infusion (P less than .05). Twenty-four-hour infusion of cisplatin resulted in greater drug retention in patients due to reduced renal clearance, but was also associated with reduced emetic toxicity, probably as a result of lower peak plasma levels.

Determinants of graft clarity in penetrating kerotoplasty.

A total of 240 consecutive penetrating keratoplasties with a minimum six months' follow-up were examined to determine the influence of preoperative prognosis, donor age, death-enucleation time, death-surgery time, and surgical experience on graft clarity. Graft results, classified as clear, nebulous, or edematous, were compared within two prognostic categories in aphakic, combined, and phakic keratoplasty groups. Preoperative prognostic groups and surgical experience appeared to be most important in affecting graft clarity, whereas the donor age, death-enucleation time, and death-surgery time seemed to have little effect.

Epithelialization of the anterior chamber after transcorneal (McCannel) suture.

A 35-year-old woman developed epithelialization of the anterior chamber with secondary glaucoma, following the use of a transcorneal (McCannel-type) suture to repair a traumatic iridodialysis. Clinical photographs and histologic documentation illustrate the potential for this serious complication from this surgical technique.

Clinical specular microscopy and intraocular surgery.

Seventy patients were studied prospectively, using the clinical specular microscope, to compare and evaluate the effects on the corneal endothelium of routine intracapsular cataract extraction (ICCE), ICCE with intraocular lens (IOL) implantation, phacoemulsification, and penetrating keratoplasty. Results showed a 6% cell loss after ICCE, 12% loss after IOL insertion, 14% after phacoemulsification, and 21% loss after penetrating keratoplasty. Both phakic and aphakic grafts had 21% cell loss. Within the aphakic keratoplasty group, there was a 10% cell loss in patients who maintained an intact vitreous face compared with a 26% cell loss in patients who underwent an anterior vitrectomy (P less than .1).

Risk management issues in radial keratotomy surgery.

In this article, reprinted from Ophthalmic Risk Management Digest, the bases for radial keratotomy-related claims and guidelines for avoiding such claims are discussed. In most lawsuits, it is not the procedure itself that is on trial, but the use of unusual technique, improper execution, or inadequacy of informed consent.

Liability issues associated with PRK and the excimer laser.

Given the elective nature of photorefractive keratectomy (PRK), the high expectations of patients, and misconceptions of the general public about refractive surgery, the use of the excimer laser for PRK opens the door to new liability risks for ophthalmologists and, in the comanagement environment, referring optometrists. The authors discuss informed consent, marketing, comanagement, and off-label use guidelines and protocols to help protect ophthalmologists against claims and better defend those that might arise.

Minocycline-induced scleral, dental, and dermal pigmentation.

PURPOSE: To report a case of scleral discoloration secondary to minocycline therapy. METHOD: Case report of a patient referred to a university-based cornea and external disease clinic. RESULTS: The patient had been treated with oral minocycline therapy for adult facial acne for 12 years when she began to develop bilateral blue-gray discoloration of the sclera as well as of the teeth, hard palate, ears, nail beds, and skin. CONCLUSIONS: Chronic systemic minocycline therapy may induce scleral pigmentary changes. The mechanism of discoloration and the long-term natural history upon cessation of minocycline are unclear.

Superficial punctate keratitis of Thygeson associated with scarring and Salzmann's nodular degeneration.

A 59-year-old woman with superficial punctate keratitis of Thygeson was observed for 14 years. The patient was treated intermittently with topical corticosteroids and artificial tears. Immediate symptomatic relief was followed by multiple recurrences and exacerbations. This case was atypical because of its prolonged clinical course and development of permanent, subepithelial corneal scarring, and elevated lesions resembling Salzmann's nodular degeneration.

Listeria monocytogenes endophthalmitis with a black hypopyon.

A 68-year-old woman had a marked decrease in visual acuity, increased intraocular pressure, and acute iridocyclitis. She developed a pigmented hypopyon simulating an occult intraocular melanoma. Two anterior chamber paracenteses showed growth of Listeria monocytogenes. The patient received systemic intravenous penicillin, topical fortified gentamicin sulfate drops, and intraocular injections of cephaloridine. On discharge from the hospital after a two-week stay, visual acuity had improved and intraocular pressure had decreased.

Aspergillus endophthalmitis after sutureless cataract surgery.

PURPOSE: We studied a case of Aspergillus endophthalmitis after sutureless cataract surgery. METHODS: A patient underwent sutureless phacoemulsification complicated by a posterior capsular tear. She subsequently developed Aspergillus endophthalmitis. Amphotericin B was injected intravitreally at the time of repeat pars plana vitrectomy. RESULTS: The eye was enucleated because of pain and poor response to treatment. CONCLUSIONS: We recommend suturing the wound in any eye that has experienced a complication of surgery.

Intrastomal corneal ring segments: reversibility of refractive effect.

PURPOSE: To evaluate the reversibility of refractive effect following removal of the ICRS (intrastromal corneal ring segments; Intacs). METHODS: Data from 34 eyes from which ICRS were removed during United States FDA Phase II and III clinical trials were evaluated with regard to segment size, loss or change of best spectacle-corrected visual acuity (BSCVA), any change of uncorrected visual acuity (UCVA), manifest spherical equivalent refraction, manifest cylinder refraction, stability of manifest cylinder refraction, and subjective visual symptoms. RESULTS: Out of 725 initial or contralateral eyes placed with the ICRS during Phase II and III clinical trials, segments were removed from 34 eyes (4.7%). Other than one (1/725, 0.1%) safety related ICRS removal, 30/725 (4.1%) were due to visual symptoms. ICRS removal was accomplished under topical anesthesia without complications in all eyes. The mean length of time the segments remained in the cornea after initial surgery was 10.3 +/- 5.4 months. At 3 months after ICRS removal, 21 eyes had monitored data available and were within +/-1 line or 10 letters of their preoperative BSCVA. Twenty eyes (20/21, 95%) returned to within +/-1.00 D of their preoperative manifest spherical equivalent refraction. All eyes had a stable refraction at the 3-month examination after removal, and a manifest spherical equivalent refraction within +/-1.00 D of their 1-month examination after removal. Nineteen eyes (19/21, 90%) returned to within +/-2 lines and 16 eyes (16/21, 76%) returned to within +/-1 line of preoperative UCVA. CONCLUSION: The ICRS (Intacs) was easily and safely removed, and eyes returned to preoperative refractive status within 3 months.

Bilateral diffuse lamellar keratitis following bilateral simultaneous versus sequential laser in situ keratomileusis.

AIM: To determine the difference in the incidence of bilateral diffuse lamellar keratitis (DLK) in patients undergoing simultaneous versus sequential laser in situ keratomileusis (LASIK) as an indication of intrinsic risk for inflammation. METHODS: A retrospective non-comparative case series of 1632 eyes that had undergone bilateral, simultaneous or sequential LASIK between April 1998 and February 2001 at a university based refractive centre by three surgeons. All cases that developed clinically evident DLK were identified and reviewed. In order to identify isolated cases and exclude those caused by environmental factors, when more than one patient in a given session developed DLK, the session was excluded. The main outcome measure was the incidence of unilateral and bilateral isolated, non-epidemic DLK. RESULTS: Of 1632 eyes, 126 eyes (7.7%) of 107 patients developed at least grade 1 DLK. In six operating sessions, DLK was observed in more than one patient per session, and on this basis 13 patients were excluded. 16 of the 94 remaining patients developed DLK in both eyes (17.0%). Six of 41 patients (14.6%) in the simultaneous group, versus 10 of 53 patients (18.9%) in the sequential group developed bilateral DLK (p >0.5). CONCLUSION: In isolated, non-epidemic bilateral DLK, a similar incidence was observed regardless of whether the surgery was simultaneous or sequential, suggesting an underlying intrinsic cause for DLK.

Long-term changes in corneal endothelium after keratoplasty. A follow-up study.

In 1983, Abbott et al. assessed endothelial cell population and function in 100 clear corneal grafts (72 patients) that were an average of 17.4 years postkeratoplasty. The present study reports on 61 of these grafts (42 patients) followed for an additional 4-6 years. Forty-nine grafts without intercurrent complications or surgery were reexamined by specular microscopy to determine the change in endothelial population in each graft. In 10 others, the reasons for regrafting were recorded. In two cases of hereditary stromal dystrophy, stromal opacity precluded a cell count. Of the grafts studied, 49 (80%) remained clear despite a depleted and slowly decreasing endothelial population. The rate of change was independent of donor age, preoperative diagnosis, or graft longevity. Two grafts failed spontaneously, and all three grafts that had cataract surgery failed in the early postoperative period. The remaining five were regrafted to correct high astigmatism or other complications. We conclude that despite a small degree of continuous cell loss, corneal grafts have a favorable prognosis for long-term clinical stability. The remaining endothelium has a minimal functional reserve, however, resulting in a high risk of graft decompensation after additional endothelial trauma.

Prospective trial of daily and extended wear disposable contact lenses.

PURPOSE: The current study prospectively evaluates the response to daily and extended wear of disposable lenses with each patient acting as his/her own control. This paradigm allowed for elimination of individual variation as a confounding factor, as well as determining whether an intrinsic factor, other than lens wear, predisposed patients to complications. METHODS: One hundred thirty-four patients were randomly assigned to contralateral daily wear (DW) or extended wear (EW) with Acuvue lenses for 1 year. All lenses were disposed of on a weekly basis. Bilateral bacteriology of lids, conjunctivae, lenses, and fingers was carried out on those patients presenting with complications. RESULTS: The results after 1 year indicate a higher incidence of complications in the EW eye (peripheral infiltrative keratopathy, 12%; corneal striae, 3%). No significant clinical complications occurred in the DW eye. Microbiological cultures did not reveal any significant difference between those eyes with keratopathy and those of controls. The most common pathogen was Staphyloccocus epidermidis. No gram-negative organisms grew from any of the culture sites. CONCLUSIONS: The results of this study indicate that extended wearing schedules, and not the lens entity, predispose the patient to a higher risk of keratopathy with disposable contact lenses. No microbiological association with the adverse events could be determined, and no intrinsic patient factor could be demonstrated that would predict the likelihood of complications.

Topical and subcutaneous alpha-interferon fails to suppress corneal neovascularization.

Corneal neovascularization is a potentially blinding complication of a variety of corneal disorders. alpha-Interferon has been shown to inhibit endothelial cell migration and proliferation. It has been used successfully in the treatment of pediatric pulmonary hemangioma and hairy cell leukemia. This study was undertaken to evaluate the effect of topical and subcutaneous (s.c.) alpha-interferon on corneal neovascularization. Corneal neovascularization was induced in 40 male New Zealand white rabbits by placing silk sutures (7.0) bilaterally in each rabbit eye at the 3 and 9 o'clock positions of the cornea, 3 mm from the limbus. Animals were randomized into two main treatment groups for topical (group 1) and s.c. (group 2) administration of interferon. Group 1 (n = 24) was then randomized into four subgroups and treated daily with topical doses of (a) rabbit specific alpha-interferon; (b) alpha-interferon plus 1% prednisolone acetate; (c) 1% prednisolone acetate; and (d) buffered phosphate control. Group 2 (n = 16) was randomized into two subgroups that received s.c. injections every other day of (a) alpha-interferon and (b) phosphate buffer. Rate of corneal neovascularization was documented photographically, with the end-point being the arrival of vessels at the suture for each group. The results of this study indicated that at the concentration and dosing regimens we used, neither topical nor s.c. alpha-interferon inhibits the rate of corneal vascular growth significantly when compared with our phosphate buffered solution control group (p = 0.88 and p = 0.84, respectively). Prednisolone acetate appeared to be the most effective in inhibiting corneal neovascularization (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

The current and future status of refractive surgery.

Kerato-refractive surgery has developed rapidly over the past decade. Many surgical procedures have been described for the correction of myopia, hyperopia, and aphakia. For the treatment of myopia, radial keratotomy has been utilized extensively. Most investigators agree that radial keratotomy results seem to be better in patients with 3 diopters or less of myopia. Keratomileusis is a complicated procedure which can correct high degrees of myopia, however, this technically difficult procedure is performed by very few surgeons in North America. Epikeratophakia for the treatment of aphakia is promising especially in the treatment of pediatric patients. The Excimer laser is evolving from a research tool to clinical reality with the coupling of the laser to computer controlled programs to reshape the cornea. The use of synthetic material inlays and intrastromal corneal ring implants are also being developed to modify the refractive status of the cornea.