Colour vision defects in asymptomatic carriers of the Leber's hereditary optic neuropathy (LHON) mtDNA 11778 mutation from a large Brazilian LHON pedigree: a case-control study.

AIMS: To determine if asymptomatic carriers from a previously identified large pedigree of the Leber's hereditary optic neuropathy (LHON) 11778 mtDNA mutation have colour vision deficits. METHODS: As part of a comprehensive analysis of over 200 members of a large Brazilian LHON pedigree spanning seven generations, colour vision tests were obtained from 91 members. Colour vision was tested one eye at a time using the Farnsworth-Munsell 100 (FM-100) hue colour vision test. The test was administered under uniform conditions, taking into account: ambient light levels, daylight colour temperature of 6700 kelvin, and neutral uniform background. Tests were scored using the FM-100 MS-Excel computer scoring program. Defects were determined and categorised as tritan, deutan, or protan. Categorisation of each dyschromatopsia was based on review of demonstrated axis computer generated plots and age adjusted error scores which coincided with Verriest 95% confidence intervals. Only the axis with the greatest magnitude error score was used to classify the defect. 55 of the 91 test subjects were LHON mtDNA 11778 J haplotype mutation carriers, proved by mtDNA analysis. The remaining 36 subjects were age matched non-blood relatives (off pedigree), who served as controls. RESULTS: 27 of 55 carriers (49.10%) were shown to have colour vision defects in one or both eyes. 13 of the 27 (48%) abnormal tests in the carrier group were tritan defects and the remaining 14 (52%) were deutan defects. Nine of the 27 (33%) abnormals in the carrier group were identified as having bilateral defects. Six of these were deutan, and the remaining three were tritan dyschromatopsias. Only six of the 36 (16.66%) age matched controls were found to have any type of dyschromatopsia. Five (83.3%) of these were deutan defects. The remaining one was a tritan defect. The difference between the two groups using a chi(2) test with one degree of freedom was statistically significant with a p value less that 0.001. CONCLUSIONS: Until now, LHON has always been characterised by a sudden, devastating vision loss. Asymptomatic carriers, those without vision loss, were considered unaffected by the disease. It now appears that asymptomatic carriers of the LHON mutation are affected by colour vision defects and may manifest other subtle, yet chronic, changes.

Corneal sensation after laser in situ keratomileusis.

PURPOSE: To report the time course for the return of corneal sensation following laser in situ keratomileusis (LASIK). SETTING: University-based retractive surgery practice. METHODS: Twenty-eight eyes of 18 patients having LASIK were evaluated. Preoperative and postoperative corneal sensation at the nasal flap hinge, at the central cornea, and within the temporal flap edge were measured before and after LASIK for a 3 week period using the Cochet-Bonnet esthesiometer (Luneau). RESULTS: Corneal sensation initially decreased in all 3 positions of the flap measured after LASIK; the greatest decrease was in the central cornea. Near preoperative corneal sensation returned by 3 weeks. The degree of sensation loss did not appear to correlate with the ablation depth. CONCLUSION: Corneal sensation is significantly decreased for approximately 2 to 3 weeks after LASIK, centrally greater than nasally at the flap hinge or temporally within the flap edge, but it generally returns to near the preoperative level by 3 weeks postoperatively.

Total skin electron beam therapy followed by adjuvant psoralen/ultraviolet-A light in the management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis fungoides).

PURPOSE: Patients with mycosis fungoides [cutaneous T-cell lymphoma (CTCL)] may benefit from adjuvant therapy after completing total skin electron beam therapy (TSEBT). We report the results for T1/T2 CTCL patients treated with adjuvant oral psoralen plus ultraviolet light (PUVA) with respect to overall survival (OS), disease-free survival (DFS), salvage of recurrence, and toxicity. METHODS AND MATERIALS: Between 1974 and 1993, TSEBT was administered to a total of 213 patients with CTCL. Records were reviewed retrospectively, and a total of 114 patients were identified as having T1 or T2 disease. Radiotherapy was provided via a 6-MeV linac to a total of 36 Gy, 1 Gy/day, 4 days/week, for 9 weeks. Beginning in 1988, patients were offered adjuvant PUVA within 2 months of completing TSEBT. This was started at 0.5-2 J/m2, 1-2 treatments/week, with a taper over 3-6 months. Therapy then continued once per month. There were 39 T1 and 75 T2 patients. Six T1 (15%) and eight T2 (11%) patients were treated with adjuvant PUVA. A further 49% of the 114 patients received adjuvant systemic therapy, 3% received spot external beam, 4% received adjuvant ECP, 2% received topical nitrogen mustard, 22% received a combination of therapies exclusive of PUVA, and 9% received no adjuvant therapy. Patients were balanced in all subgroups based on pre-TSEBT therapy. The median age of the cohort was 58 (range 20-88), with a median follow-up time of 62 months (range 3-179). RESULTS: Within 1 month after completing of TSEBT, 97% of T1, and 87% of T2 patients had achieved a complete remission. Stratified by adjuvant therapy, none of six T1 and one of eight T2 patients who received adjuvant PUVA failed within the first 3 years after completion of TSEBT. A total of 43% of the T1 and T2 patients receiving other or no adjuvant treatment failed within the same time course. The 5-year OS for the entire cohort was 85%. Those who received PUVA had a 5-year OS of 100% versus a 5-year OS for the non-PUVA group of 82% (p < 0.10). The 5-year DFS for the entire cohort was 53%. Those who received PUVA had a 5-year DFS of 85% versus a 5-year DFS for the non-PUVA group of 50% (p < 0.02). By T stage, those with T1 receiving PUVA exhibited no relapses, whereas those with T1 not treated with PUVA had a crude relapse rate of 36%. Median DFS was not reached at 103 months for the T1 adjuvant PUVA patients versus 66 months for the non-PUVA patients (p < 0.01). For those with T2, crude relapse rates were 25% and 55%, respectively, with DFS of 60 (median DFS not reached) and 20 months (p < 0.03). The 5-year DFS for patients salvaged with PUVA was 50%. Toxicity of adjuvant and salvage PUVA therapy was acceptable, with only two patients requiring a reduction in PUVA dosage. CONCLUSION: PUVA can maintain remissions in patients with CTCL after TSEBT. There is a significant benefit in DFS but no statistically significant improvement in OS. Prospective, randomized data are needed to confirm these results. PUVA is also effective as a salvage therapy after TSEBT in early-stage patients with recurrence, with acceptable toxicity.

Additional courses of total skin electron beam therapy in the treatment of patients with recurrent cutaneous T-cell lymphoma.

BACKGROUND: Recurrent cutaneous T-cell lymphoma (CTCL) is managed with a variety of modalities. Repeat treatment with additional courses of total skin electron beam therapy (TSEBT) has not been formally evaluated. OBJECTIVE: Our purpose was to evaluate the efficacy and toxicity of additional TSEBT for recurrent CTCL. METHODS: A total of 14 patients were treated with TSEBT and received at least two courses, with five of those patients receiving a third course. Patients were offered additional TSEBT if they suffered recurrence despite other therapy if the extent of the recurrence precluded localized radiation. The median follow-up was 36 months. RESULTS: The median dose for the entire group was 57 Gy. Thirteen patients (93%) achieved a complete response (CR) after the initial course. After the second course, 12 patients (86%) had a CR; of the five patients who underwent a third course, three (60%) achieved a CR. The median disease-free interval after the first course of therapy for those with a CR was 20 months and 11.5 months after the second course. Median survival after the second course was 15 months. All patients had xerosis, pruritus, desquamation, mild erythema, epilation, and anhidrosis of the skin. CONCLUSION: Patients with recurrent CTCL recalcitrant to other forms of therapy or too diffuse for treatment with localized radiation fields are candidates for additional TSEBT. This therapy is effective and well tolerated with an acceptable risk profile.

Extent of skin involvement as a prognostic indicator of disease free and overall survival of patients with T3 cutaneous T-cell lymphoma treated with total skin electron beam radiation therapy.

BACKGROUND: The goal of this study was to define the prognostic significance of the extent of skin involvement (ESI) with respect to disease free survival (DFS) and overall survival (OS) of patients with T3 cutaneous T-cell lymphoma (CTCL) after total skin electron beam therapy (TSEBT). METHODS: Between 1974 and 1993, TSEBT (36 Gray [Gy], 1 Gy/day for 9 weeks, 6 MeV electrons) was administered to a total of 213 patients. Forty-six of the 213 patients were classified as having T3 CTCL based on the presence of tumor nodules on the skin at diagnosis. Patient records were evaluated retrospectively, and the percentage of total skin surface involved was calculated. Patients were analyzed with respect to response to therapy, disease free and overall survival. The median follow-up was 37.5 months (range, 1.6-93 months). RESULTS: Thirty-six of 46 patients achieved complete clinical response (CCR) by the completion of TSEBT. DFS was 12% at 36 months with approximately 28% OS. When stratified by extent of skin involvement, 100% of patients with 9% or less ESI were disease free at 18 months compared with patients with 10% or greater ESI, all of whom had relapsed by 18 months (78% achieved CCR). Fifty percent of those with 9% or less ESI remained disease free at 36 months; median DFS and OS were not reached at 63 and 65 months, respectively. The median DFS and OS for the 10% or greater ESI group were 4 and 24 months, respectively. These differences were statistically significant (P < or = 0.005). Toxicity of therapy was minimal. CONCLUSIONS: The extent of skin involvement of patients with T3 CTCL is a prognostic indicator of disease free and overall survival for those who have been treated definitively with TSEBT.