Photorefractive keratectomy in a patient with Stargardt disease: Case report

Abstract

This case presents a successful outcome following photorefractive keratectomy surgery in a patient with Stargardt disease. A 23-year-old female with a history of Stargardt disease oculus uterque and high myopia oculus uterque presented for refractive surgery evaluation. The patient underwent photorefractive keratectomy oculus uterque. Before surgery, the patient’s refraction was −6.00 diopters oculus uterque. Visual acuity was 20/200 with correction oculus uterque. After photorefractive keratectomy, visual acuity improved to 20/100 oculus uterque without correction at 7 days post-op. At 1 year post-op, visual acuity remained stable at 20/100 +1 oculus dexter and 20/200 +1 oculus sinister without correction. Electroretinography pre- and postoperatively was stable. The patient reported subjective improvement in vision at all time points after the procedure, likely due to the resolution of minification from previous corrective lenses. While photorefractive surgery is not a definitive treatment for Stargardt disease, Stargardt disease is not a contraindication for photorefractive keratectomy surgery. This case presents successful refractive correction without retinal complications. We suggest that performing photorefractive keratectomy in a patient with Stargardt disease is unlikely to cause harm due to disease exacerbation based on this study and previous studies on the interaction of photorefractive keratectomy with corneal, lens, and retinal level outcomes. Though a soft visual endpoint may pose a unique challenge for refractive surgery in Stargardt disease, we report effective use of the iDesign 2.0 software. In all, we postulate that refractive surgery such as photorefractive keratectomy is likely to improve quality of life and vision in patients with Stargardt disease and possibly other inherited retinal pathologies as well.

Introduction

Stargardt disease (STGD) is the most common form of inherited macular degeneration, caused by autosomal recessive mutations in the ABCA4 gene. The disease affects children and young adults and is marked by the accumulation of lipofuscin in the retinal pigment epithelium; this leads to degeneration of photoreceptors and progressive central vision loss. There is no definitive treatment for STGD to date, although avenues including gene therapy and deuterated vitamin A are being explored. ¹ Photorefractive keratectomy (PRK) is an excimer laser procedure developed to correct refractive errors. PRK does not directly address the macular degeneration of STGD – as the surgery works at the corneal level. No previous cases in the literature report the successful and safe use of PRK in patients with STGD or other inherited retinal diseases. However, inherited retinal disease is not a contraindication to PRK in patients with STGD and concurrent refractive errors. ² To perform PRK, the patient must have stable refraction, adequate corneal thickness, normal corneal topography, absence of ocular surface disease, no significant cataracts, and no active infections or inflammation. ³

Case report

Our patient is a 23-year-old female with a history of STGD oculus uterque (OU) and severe myopia OU who presented for refractive surgery evaluation. The patient’s STGD was double allele ABCA4 genotype proven with two different mutations, p.Arg2107Cys:c.6319C>T and p.Gly607Arg:c.1819G>A. She was being followed with stable visual acuity of 20/200 with correction OU and stable macular exam findings of STGD. The patient also had a history of bilateral optic nerve hypoplasia, labile intraocular pressure (IOP), and ocular hypertension without glaucoma. Her ocular hypertension was diagnosed 2 months prior to surgery with IOP of 26 mmHg oculus dexter (OD) and 29 mmHg oculus sinister (OS), mild ocular nerve head cup asymmetry but healthy rim tissue, and normal optical coherence tomography retinal nerve fiber layer OU. She was not on any ocular medications.

At evaluation, uncorrected visual acuity was counting fingers at 3 feet OU with the best correction to 20/200 OU with a manifest refraction (MRx) of −6.50 +0.75 × 091 OD and −6.00 +0.25 × 093 OS. The iDesign WF Rx was −6.30 +0.71 × 091 at 12.50 mm OD and −6.12 +0.32 × 095 at 12.50 mm OS. There was a physician adjustment of −0.20 D OD and +0.12 D OS. Adjusted corrections became: −6.50 +0.71 × 091 OD and −6.00 +0.32 × 093 OS. From the autorefractor keratometry, K1 was 43.25 D, K2 44.25, and K2 Axis 77° OD, and K1 was 43.25, K2 43.75, and K2 Axis 99° OS. Corneal thickness was 534 OD and 542 OS (Figure 1). IOP was 18 mmHg OD and 21 mmHg OS. Optical zone was 6.3 × 6.0 mm OD and 6.1 × 6.0 mm OS. The ablation zone was 8.0 mm OU. The risks, benefits, and alternatives to surgery were discussed. Patient-specific benefits included the potential elimination of the need to wear corrective lenses and possible improvement of significant minification due to the patient being a high myope. However, the discussion also included the fact that vision potential would be limited by STGD.

Figure 1.

Pentacam corneal morphology.

The patient elected to proceed with PRK OU due to possible glaucoma suspicion and IOP lability OU. An Amoil’s brush (Innovative Excimer Solutions, Inc., Toronto, ON, Canada) with a hyperopic head was used for epithelial debridement. Excimer treatment was performed with a VISX S4 (J&J Vision, Irvine, CA, USA) with iris registration using the treatment calculated with the iDesign 2.0 software (J&J Vision, Irvine, CA, USA). Mitomycin C 0.02% was applied for corneal haze prophylaxis. There were no complications during the procedure. An Acuvue Oasys (J&J Vision) bandage contact lens was applied bilaterally, and the patient was discharged on moxifloxacin 0.5% OU QID, fluorometholone 0.1% OU QID, and ketorolac 0.5% OU BID. Pain control regimen included oral ibuprofen 800 mg TID and a needed combination of acetaminophen/codeine. Instructions were given to apply ice packs to closed eyes for 20 min/waking hour for the first 2 days postoperatively.

On post-op day 7, visual acuity improved to 20/100 OU without correction (sc). The corneal epithelium was healed and clear with few punctate stains. Bandage contact lenses were removed, and a taper of fluorometholone over 3 weeks was started. The patient was instructed to utilize artificial tears QID. At this visit, the patient stated she felt her vision had improved, and she was finding more clarity in tasks such as cleaning.

At 1 month, visual acuity improved further to 20/70 OD and 20/80 OS sc. The corneal epithelium was completely healed. The patient experienced ocular hypertension to 24 mmHg OU (not adjusted for corneal thickness), which was presumed to be related to the fluorometholone taper and normalized once off the medication. The patient reinforced that she felt her vision was much improved.

At 1 year, visual acuity was 20/100 +1 OD and 20/200 +1 OS sc. The patient felt her vision was stable. Given the patient’s limited vision, a soft refractive endpoint was noted without improvement despite attempts at careful refraction. This patient was not interested in wearing spectacles or considering an enhancement as she was satisfied with the postoperative vision.

At 16 days pre-op, a dilated exam revealed retinal flecks OS > OD. The same finding was noted on exam at 1 year post-op (Figure 2). Electroretinography (ERG) pre- and postoperatively was stable (Figure 3).

Figure 2.

(a) Macular OCT, 16 days preoperative. (b) Macular OCT, 1 year postoperative.

Figure 3.

(a) Multifocal electroretinogram, 7 days preoperative. (b) Multifocal electroretinogram, 6 months postoperative.

Discussion

In the determination of whether to perform PRK on a patient with STGD, there are several important considerations. First, there is the consideration of safety. PRK has been shown to be safe in many disorders of the cornea. Moshirfar et al. were the first to study laser-assisted in situ keratomileusis (LASIK) in two patients with posterior polymorphous dystrophy (PPMD), and they found only a small mean endothelial cell loss (2.3%) at 1 year with no adverse events and uncorrected visual acuity (UCVA) equal to or better than 20/25. ⁴ Bower et al. studied 14 eyes with PPMD who underwent PRK. There were no significant complications, and at 1 year post-op, all eyes were within ±0.5 diopter of emmetropia. ⁵ Ratanasit et al. studied five eyes in which Descemet stripping automated endothelial keratoplasty (DSAEK) was performed for Fuchs corneal dystrophy and pseudophakic bullous keratopathy (PBK); this was followed by PRK or LASIK at around 1 year after DSAEK. Postoperative UCVA improved to 20/20–20/40 from 20/80 to 20/200, and all grafts remained clear. ⁶ In the aforementioned study, BSCVA remained stable, but it is relevant to note that Moshirfar et al. and Dastjerdi and Sugar suggest that severe corneal guttata may be a contraindication to LASIK surgery due to the development of transient corneal edema and loss of BSCVA.^7,8 However, these patients lacked DSAEK prior to refractive surgery, suggesting that correction of the dysfunctional endothelial layer prior to refractive correction may be a protective factor.

The literature has also shown that the excimer laser used in PRK and LASIK is not linked to the formation of premature cataracts. Wachtlin et al. performed PRK and LASIK in 12 eyes of white Russian rabbits. They removed the lenses 2 weeks later and looked for higher malondialdehyde levels, which are thought to be related to cataractogenesis. While PRK lenses did not have increased levels, some LASIK lenses did; however, this was attributed to postoperative inflammation due to concurrent microkeratome incision. ⁹ We can also note that the cornea and lens provide significant protection against UV radiation.^10,11 As the excimer laser utilizes UV light, this radiation is unlikely to travel as far back as the retina.

PPMD is an inherited disorder of the corneal endothelium and Descemet’s membrane. ¹² Fuchs dystrophy is a sporadic or inherited dysfunction of the corneal endothelium. ¹³ Finally, PBK is persistent corneal edema following cataract surgery, caused by corneal endothelial trauma. ¹⁴ All these pathologies occur at the innermost layers of the cornea. In a healthy cornea, Descemet’s membrane is 500–600 µm from the surface of the cornea. ¹⁴ The anterior surface of the lens is around 3.11 mm from the corneal surface, and the posterior pole of the retina is 24 mm from the corneal surface.^14,15 Therefore, since the literature supports that PRK avoids causing complications of the cornea and lens, it is plausible to postulate that PRK would not impact retinal pathology.

While retinal detachment following PRK in high myopes has been noted, the incidence reported by Ruiz-Moreno et al. was 0.08%, a rate similar to high myopes not having refractive surgery. ¹⁶ Case reports of retinal detachment following LASIK surgery do exist, but most report this occurrence in high myopes. There is one report of macular hemorrhage occurring after PRK in three patients, again all with high myopia. ¹⁷ Of note, there is one case report of a patient who was not a high myope who experienced bilateral macular holes following PRK. ¹⁸ Interestingly, there was a study done to evaluate the development of choroidal neovascularization after PRK. Including 5936 eyes, it found that while choroidal neovascularization is a potential complication for myopic eyes, the risk of development did not increase post-PRK. ¹⁹ There is no current literature that suggests PRK exacerbates disease progression in STGD. Our patient had no complications with stable visual acuity before and 1 year after surgery. She also had stable retinal exam findings and ERG results pre- and postoperatively.

Another consideration centers around the fact that vision potential is limited due to retinal pathology. PRK does not correct the cause of STGD, and, for this reason, it is likely that the natural history of STGD will be unaffected by the performance of PRK. There are benefits to PRK in terms of quality of life and vision, though, as evidenced by our patient’s reported satisfaction and perceived improvement in vision. She was able to stop wearing corrective lenses; this benefit was accompanied by the elimination of minification in her case of severe myopia. The patient’s preoperative refraction of −6.25 diopters would have resulted in a 12.5% reduction in image size while wearing corrective lenses. When minification is significant, discomfort, altered perception of motion, and dizziness can result. ²⁰ After PRK, this minification was significantly reduced, and the patient’s environment would have seemed magnified. This was likely a factor in our patient’s perceived improved postoperative quality of vision despite a persistent limited quantity of vision.

Finally, it is relevant to note that patients with STGD have a soft visual endpoint. ²¹ In other words, they may be unreliable in determining slight differences in visual quality when using the phoropter. This is important in refractive surgery to make precise changes. In our case, the use of the iDesign 2.0 software helped provide a more objective measure. Calculations created by iDesign can be checked against the phoropter for comparison.

Important considerations must be stated as to the limitations of our report. First, we did not utilize any standardized questionnaire to formally interrogate qualitative visual improvement and did not employ methods such as contrast sensitivity, higher-order aberrations, modulation transfer function, or other visual quality metrics such as ocular scatter index. Second, we were only able to follow this patient for 1 year postoperatively. Therefore, long-term stability of myopic correction is unknown.

Conclusions

Based on our case and supporting literature, we suggest that performing PRK in a patient with STGD is unlikely to cause harm due to disease exacerbation and likely to improve quality of life and vision, especially in cases of high myopia. In addition, the iDesign 2.0 software allows for the management of the soft visual endpoint in STGD. With more studies, we hope the ideas presented in this case might be generalized to inherited retinal pathologies beyond STGD.