Purpose
To investigate the functional and morphologic midterm outcome of phototherapeutic keratectomy (PTK) for Thiel-Behnke corneal dystrophy diagnosed by gene-mutation analysis.
Design
Retrospective, single-center clinical study.
Methods
Between July 2001 and May 2010, 10 consecutive PTKs were performed in 10 eyes of 5 patients (2 male, 3 female; mean age: 55 ± 13 years) with superficially accentuated opacities caused by Thiel-Behnke corneal dystrophy and were followed up for at least 12 months (range: 12–108 months). Main outcome measures included (1) best-corrected visual acuity (BCVA), (2) uncorrected visual acuity (UCVA), (3) spherical equivalent, and (4) recurrence rate. The probability of recurrence of Thiel-Behnke corneal dystrophy after PTK was calculated using the Kaplan-Meier method for survival analysis.
Results
The p.Arg555Gln mutation was found within the TGFBI gene in all 5 patients. Average logarithm of minimal angle of resolution (logMAR) BCVA change was −0.55 ± 0.26. Average logarithm UCVA change was −0.54 ± 0.31. In 5 of the 10 eyes, recurrence of central superficial opacification was clinically identified during the follow-up periods, and in 4 of those 5 eyes, the level of the recurrence was so significant that the visual acuity was reduced more than 2 lines. The maximum follow-up period of the 1 eye without significant post-PTK recurrence was 108 months.
Conclusions
PTK is a successful therapy for Thiel-Behnke corneal dystrophy, and results in midterm stable visual acuity and corneal transparency. Unlike in Reis-Bücklers corneal dystrophy cases, PTK delays the need for more invasive surgical intervention in Thiel-Behnke corneal dystrophy.
Thiel-Behnke corneal dystrophy, also known as “honeycomb” corneal dystrophy, is an autosomal dominant inheritable disease and was described as corneal dystrophy of the Bowman layer and superficial stroma type II (CDB II, OMIM# 602082 ) in a report by Küchle and associates. Recent molecular biological analysis has revealed that this dystrophy is caused by the missense mutation (p.Arg555Gln) of the human transforming growth factor beta–induced ( TGFBI ) gene.
Characteristic bilateral, subepithelial corneal opacities, frequently accompanied by recurrent corneal erosions, normally appear in Thiel-Behnke corneal dystrophy patients between the ages of 10 and 20 years. This disease runs a slow progressive course, with painful erosive episodes and gradual deterioration of vision. The treatment modalities for this disease include superficial keratectomy, lamellar keratoplasty, penetrating keratoplasty (PKP), and phototherapeutic keratectomy (PTK).
In Japan, the Ministry of Health, Labour and Welfare approved the medical use of 193-nm argon-fluoride excimer laser devices for PTK procedures in 2000. Since then, PTK has been applied for the treatment of various types of corneal diseases, including inheritable corneal dystrophies, band keratopathy, recurrent corneal erosion, certain types of degenerative corneal diseases (eg, Salzmann’s degeneration), and bullous keratopathy. The PTK procedure is generally thought to produce the best results when it is used for the ablation of corneal opacity restricted to the anterior stroma of the cornea. When PTK is performed on patients who have passed strict diagnostic criteria, the satisfaction level in relation to the results of this procedure is reportedly very high.
The purpose of this retrospective, single-center clinical study was to investigate the functional and morphologic midterm outcome of PTK performed in multiple Thiel-Behnke corneal dystrophy patients who were strictly diagnosed through the use of gene mutation analysis.
Methods
Study Population
This study involved 10 consecutive PTKs performed in 10 eyes (5 right eyes and 5 left eyes) of 5 patients (2 male and 3 female) to treat superficially accentuated opacities that were clinically and genetically diagnosed as Thiel-Behnke corneal dystrophy between July 13, 2001 and May 14, 2010. Only the patients who were followed up for at least 12 months after the PTK surgery were enrolled in this study. The mean age of the patients was 55 ± 13 years (range: 32–66 years). None of the enrolled patients had any previous history of corneal surgery. The PTK surgery was performed for the patient’s visual rehabilitation at the time when the patient complained of decreased vision or when the patient’s best-corrected visual acuity (BCVA) had become worse than logMAR 0.15. Each of the 5 patients had experienced painful erosive episodes prior to undergoing the surgery. Three of the 5 patients were members of the same pedigree.
Molecular Analysis
Peripheral blood samples were collected from all 5 patients after they had received a complete, detailed explanation of the study protocols. DNA was extracted from the peripheral blood lymphocytes using a commercially available kit (DNeasy Blood & Tissue Kit; QIAGEN GmbH, Hilden, Germany). Exons 4, 11, 12, and 13 of the TGFBI gene, as well as their flanking introns, were amplified by polymerase chain reaction (PCR) and directly sequenced on both strands using previously published primers.
Interventional Procedure
PTK was performed by the use of 1 of 3 commercially available 193-nm excimer laser devices, each produced by a different company. Five eyes were treated using the EC-5000 excimer laser (NIDEK Co Ltd, Gamagori, Japan), 3 eyes were treated using the VISX S4IR excimer laser (Abbott Medical Optics Inc, Abbot Park, Illinois, USA), and the remaining 2 eyes were treated using the Technolas T-217z Zyoptix laser system (Bausch & Lomb, Rochester, New York, USA). In all 10 eyes, the epithelium was removed directly by the excimer laser, and the ablation continued into the corneal stroma until approximately 50 μm of the stromal ablation was performed. During the surgery, the cornea of each eye was examined by use of the microscope equipped in the excimer laser devices under sclerotic scattering illumination using a vitrectomy-endoilluminator placed on the limbus. When deemed necessary, additional ablations were performed to remove the bulk of the pathologic opacity from the visual axis. For all 10 eyes, the ablation was performed until the majority of opacities were removed, thus resulting in a mean calculated total ablation depth (including epithelium and stroma) of 116 ± 12 μm (range: 100–140 μm). Masking fluid was not used. Postoperatively, all 5 patients were initially administrated 0.1% fluorometholone (FLUMETHOLON; Santen Pharmaceutical Co, Ltd, Osaka, Japan) and 1.5% levofloxacin hydrate (CRAVIT; Santen Pharmaceutical Co, Ltd) 4 times daily, with a tapering-off of the dosage over 12 weeks. Each patient was instructed to continually wear a soft contact lens on the operated cornea until the epithelial defect had closed.
Main Outcome Measures
In this present study, main outcome measures including BCVA, uncorrected visual acuity (UCVA), spherical equivalent (SE), and recurrence of Thiel-Behnke corneal dystrophy were assessed.
Clinical Definition for Recurrence of Thiel-Behnke Corneal Dystorphy Post–Phototherapeutic Keratectomy
The recurrence of Thiel-Behnke corneal dystrophy was considered significant when slit-lamp examination showed signs of increased central opacification of the superficial cornea that were also associated with significant visual loss (a 2-line or more loss of BCVA) according to the previous study. The probability of recurrence of Thiel-Behnke corneal dystrophy after PTK surgery was calculated using the Kaplan-Meier method for survival analysis.
Statistical Analysis
For analysis of the results, Excel Tokei 2002 statistics software (SSRI Co Ltd, Tokyo, Japan) was used. Differences between paired samples were analyzed with the paired t test. A probability value of <.05 was considered statistically significant.
Results
The p.Arg555Gln mutation was found within the TGFBI gene in all 5 patients. In all 5 patients, the superficial corneal opacities were successfully removed from the corneal visual axis ( Figure 1 ). In all 10 eyes, epithelial defects closed within 3 to 5 days and visual acuity gradually improved in 3 to 24 months after the surgery ( Table .). The mean follow-up period was 60 ± 46 months (range: 12–108 months). Postoperatively, all 5 patients requested to have PTK surgery performed to their contralateral eyes, thus indicating that they were satisfied with the results of the initial PTK surgery.
| Patient a | Age (y) | Sex | Eye | BCVA (logMAR) | Calculated Ablation (μm) | (Month) | ||
|---|---|---|---|---|---|---|---|---|
| Preoperative | Postoperative b | T1 | T2 | |||||
| 1 | 57 | F | R | 0.52 | −0.18 | 113 | 1 | 108 |
| 1 | 65 | F | L | 0.70 | 0.10 | 100 | 12 | 12 |
| 2 | 32 | M | R | 0.22 | −0.08 | 100 | 3 | 108 |
| 2 | 32 | M | L | 0.15 | −0.08 | 110 | 3 | 108 |
| 3 | 57 | F | R | 0.52 | 0.05 | 114 | 24 | 96 |
| 3 | 57 | F | L | 1.22 | 0.15 | 120 | 3 | 96 |
| 4 | 66 | M | R | 0.70 | −0.08 | 120 | 12 | 18 |
| 4 | 66 | M | L | 0.70 | 0.22 | 121 | 12 | 18 |
| 5 | 61 | F | R | 0.52 | 0.15 | 140 | 6 | 18 |
| 5 | 61 | F | L | 0.52 | 0.10 | 125 | 3 | 18 |
a Patients 2, 3, and 5 were blood relatives.
b Postoperative BCVA denotes the best overall BCVA after surgery.
A 2-line or more increase in BCVA was found in all of the 10 enrolled eyes after the PTK surgery. The mean logMAR BCVA improved from 0.57 ± 0.29 preoperatively to the overall best of 0.04 ± 0.13 postoperatively, which was statistically significant ( P < .001). The mean UCVA also significantly improved, from logMAR 0.84 ± 0.34 preoperatively to the overall best of logMAR 0.30 ± 0.26 postoperatively ( P < .01). The average logMAR UCVA change was −0.54 ± 0.31.
The mean SE significantly increased from −1.63 ± 2.74 diopters (D) preoperatively to 0.43 ± 2.13 D postoperatively, which was statistically significant ( P < .01). The average refractive change was +2.05 ± 1.68 D (range: −0.25 to +5.75 D). There was no apparent difference in the SE changes in relation to the type of excimer laser device used or to the calculated ablation depths ( Figure 2 ).
Postoperative complications such as infection, delay in epithelial healing, or stromal haze were not noticed in any of the 10 eyes, and none of the patients experienced any postoperative painful erosive episode. During the follow-up period, 5 of the 10 eyes experienced recurrence of the central superficial opacification. One of those 5 eyes (the right eye of Patient 2) had only a 1-line decrease of visual acuity at 108 months postoperatively ( Figure 3 ). However, in 4 of those 5 eyes, the degree of recurrence was significant enough to lead to a decrease in visual acuity of more than 2 lines, yet none of those patients requested a PTK reoperation at their final follow-up visit. The earliest significant recurrence (the right eye of Patient 3) was observed after 42 months ( Figures 4 and 5 ). The remaining 5 of the 10 eyes exhibited no apparent signs of recurrence, possibly because the follow-up period for those eyes was not very long.
