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Outcome of Pediatric Cataract Surgery in Patients Who Have Undergone Bone Marrow Transplantation

Purpose: Bone marrow transplantation (BMT) and pre-treatment conditioning increases the risk of developing pediatric cataracts. We present the outcome of cataract surgery in children who have had BMT. Methods: We conducted a retrospective chart study with 15 BMT patients (28 eyes) who underwent cataract extraction between 2002 and 2012. Outcome measures include change in best corrected visual acuity (BCVA) and complications. Results: 7 (47%) patients had acute lymphoid leukemia, 3 (20%) had acute myeloid leukemia, 2 (13%) had myelodysplastic syndrome, 1 (7%) had Fanconi anemia, 1 (7%) had juvenile myelomonocytic leukemia, and 1 (7%) had adrenoleukodystrophy. Patients received BMT at a mean age of 3.9 ± 1.6 years. 12 (80%) patients received total body irradiation (TBI) and 3 of these 12 received cranial irradiation in addition to TBI; one (7%) received only cranial irradiation. Total body irradiation included head and eye exposure. Mean age of cataract surgery was 9.1 ± 2.3 years; mean follow-up was 55.9 ± 45.1 months. All cataracts were of posterior subcapsular subtype. Mean BCVA improved from 0.7 ± 0.4 logMAR to 0.3 ± 0.5 logMAR (p < 0.001). 23/28 eyes (80%) had cataract extraction with intraocular lens placement; 5/28 (20%) of the eyes had cataract extraction with primary posterior capsulotomy and anterior vitrectomy (PC/AVx). 23/23 (100%) of the eyes without primary PC/AVx developed PCO an average of 2.3 ± 6.9 months after surgery. No eyes with primary PC/AVx eyes developed PCO. Conclusions: Children with history of BMT have a predisposition of developing posterior subcapsular cataracts and have a high rate of visually significant PCO if the posterior capsule is left intact at the time of cataract surgery.


Introduction
Bone marrow transplantation (BMT) with pre-treatment conditioning is an established treatment for childhood leukemia, myelodysplastic syndrome and other hereditary and metabolic hematologic disorders. While BMT has increased life-expectancy for children with hematologic disorders, this life-saving intervention has a number of sequelae including cataract formation. Common conditioning pre-treatments for BMT include irradiation, corticosteroid treatment, and chemotherapy, each of which have been independently observed to be associated with increased cataract formation [1] [2] [3] [4] [5]. A number of studies have found that total body irradiation (TBI), compared to chemotherapy and corticosteroids, is likely the most significant factor for developing cataracts in patients who received BMT [6]- [11].
Although pediatric cataracts occur frequently in patients who have had BMT, there is limited data in the literature regarding the surgical outcome of cataracts in these patients. This study aims to characterize the cataracts that develop in pediatric bone marrow transplant patients and describe the complications and visual outcomes of cataract surgery in these patients.

Materials and Methods
Prior to initiating this study, institutional review board approval was obtained from the Baylor College of Medicine. A comprehensive database search of our electronic medical record was performed to identify all patients under the age of 18 with history of BMT who had cataract surgery between September 25, 2002 and December 4, 2012. Patients were excluded if BMT was received at an outside institution, or if the patient had less than 1 month of follow-up after cataract surgery.
For patients unable to cooperate in clinic, intraocular lens calculations were performed in the operating room using immersion A-scan ultrasonography for axial length measurements and keratometry was obtained using a handheld keratometer. Cataract surgery was performed using standard technique [12] [13].
Briefly, in cases in which the posterior capsule was left intact, a temporal clear corneal incision was made using a keratome and a continuous curvilinear capsulorrhexis was performed with utrata forceps; aspiration of the lens was accomplished using an automated irrigation/aspiration handpiece with the Accurus system (Alcon Laboratories). In patients in which a primary posterior capsulotomy and anterior vitrectomy was planned, the anterior capsulotomy and lens aspiration were performed using a mechanical vitrectomy handpiece using bimanual technique. Primary posterior capsulotomy and anterior vitrectomy through the pars plana approach was then performed in a standard fashion after placement of the intraocular lens [14].
The optic and haptics were placed in the capsular bag. All patients were treated postoperatively with prednisolone acetate 1% eye drops every 2 hours for the

Results
A total of 31 eyes in 18 patients who had cataract surgery after BMT were identified. Two patients were excluded because they received BMT at outside institutions and one patient was excluded due to not returning for any post-operative visits. Therefore, twenty-eight eyes in 15 patients met the criteria for inclusion.
All cataracts were of the posterior subcapsular subtype. Mean best corrected visual acuity (BCVA) improved from 0.7 ± 0.4 logMAR (Snellen 20/100) pre-op to 0.3 ± 0.5 logMAR (Snellen 20/40) at most recent visit (p < 0.001). Twenty-four of 28 eyes (85.7%) had improved visual acuity with Snellen BCVA of 20/40 or better at the most recent visit. Two of the eyes that did not improve belonged to a patient with bilateral optic atrophy due to leukemic infiltration. The other two eyes belonged to a patient with severe keratoconjunctivitis sicca due to GVHD; this patient also had a corneal scar in one eye which developed after a microbial keratitis.  Other associated ocular conditions noted were myelinated nerve fibers in one eye, bilateral optic atrophy in one patient, and keratoconjuntivitissicca with 2 patients. As described above, one of the patients with keratoconjunctivitis sicca also had a corneal scar from a treated microbial keratitis. One patient had an exotropia which was corrected with surgery.

Discussion
We found that patients with cataracts which develop after BMT and conditioning treatment have a predisposition to develop posterior subcapsular type of cataracts. Other studies have also found that patients with a history of BMT have a propensity to develop cataracts of the posterior subcapsular type [7] [9] [11].
In previous studies, it has been found that BMT patients typically developed cataracts within 4 years of transplantation [6]- [11]. This is consistent with our pop-  [9]. It is likely that the development of cataracts in patients after BMT is multifactorial, as many of these patients are ex-A. Chen, K. G. Yen Open Journal of Ophthalmolog posed to a variety of treatments including TBI, cranial irradiation, and systemic steroids. This is further supported by the fact that, in our series, there were two patients who did not receive either TBI or cranial irradiation.
The patients in our study had improvement in visual acuity after cataract extraction from an average Snellen BCVA 20/100 pre-operatively to 20/40 at the most recent visit. Other studies examining cataract extraction after BMT also observed improvement in BCVA after surgery [7] [8]. The two patients who had vision worse than 20/40 had ocular comorbidities. One patient had bilateral optic atrophy and had visual acuity of count fingers in both eyes. The other patient had a corneal scar in the right eye and severe keratoconjunctivitis sicca due to graft versus host disease. The high rate of visually significant PCO after cataract surgery in our patients is comparable to other studies examining patients with cataracts after BMT. Calissendorff and Bolme and Frisk, et al. showed that the majority of their patients who had cataract extractions after BMT needed Nd:YAG laser capsulotomy within 3 years of surgery and that the patients were able to achieve good visual acuity and outcome after the laser treatment [7] [8]. In Frisk, et al., of the 10 eyes that received cataract extractions and intraocular lens implants, 6 eyes needed YAG laser a median of 1.5 years after cataract extraction [8]. In Calissendorff and Bolme, 28 eyes received surgery with the majority requiring YAG laser within 2 years after surgery; however, the number of patients and time period in which the PCO developed was not specified [7]. The authors did note that cleaning the capsule intraoperatively was, in most cases, impossible with risk of causing posterior capsular breakage [7]. In our study, 78% of our patients with an intact posterior capsule developed visually significant PCO within the study time period. Although irradiation dosage was not available for all patients, in the patients for which the data was available, those with higher dosage developed PCO sooner. We also found that 91% (21/23) of the eyes with posterior capsule left intact were found to have PCO intraoperatively with inability to completely polish the capsule completely without risk of damaging the posterior capsule. The opacification of the capsule in these patients appeared to be integrated within the capsule, perhaps in the form of capsular fibrosis, although histologic examination of the capsule was not performed and would likely be difficult to complete.
Many studies have examined rates of PCO development in children with con- It is worthwhile to note that of the 5 patients who had primary PC/Avx, none developed VAO in the study time period. In patients who would not be cooperative for a Nd:Yag laser, primary PC/Avx could therefore save the patient a second intraocular procedure soon after the first. In older, cooperative patients, however, Nd:YAG laser treatment easily corrected PCO with good visual outcomes; counseling parents and patient regarding the potential need for Nd:YAG laser soon after surgery, would be appropriate in this patient population. Recurrence of PCO, which has been reported in the pediatric population [27], appears low in these patients. Only one patient required a second treatment and this patient achieved a good outcome.
Our study was limited by its retrospective nature and the small sample size as well as variable follow-up times, and lack of a control group. Ideally, treatment outcomes and complications should be assessed over many years. Irradiation dosage for TBI and length of steroid treatment would be useful to determine if there is a relationship between PCO development and these treatments. However, this data was not available for all patients due to older BMT records not being available for many of the patients.

Conclusion
Pediatric patients with history of BMT and pre-conditioning treatments are more likely to have cataracts of the posterior subcapsular cataract type; surgical treatment of these cataracts is associated with few complications and good visual outcomes. The rate of development of visually significantly PCO is high in this patient population with many patients having changes that appeared integrated with the posterior capsule and which cannot be polished intraoperatively. Although a primary posterior capsulotomy with anterior vitrectomy is effective in reducing the rate of developing visual axis opacification, Nd:YAG laser is an effective treatment for these patients and the posterior capsule can be left intact without consequence if the patient can be cooperative for this procedure.