Transscleral Diode Photocoagulation of Large Retinal and Choroidal Vascular Lesions

Background Transscleral retinal photocoagulation with a diode laser is used in glaucoma refractory to medical and surgical treatment. Our main research question was how the technique performed in large vascular lesions associated with hemangiomas of the retina and choroid. Methodology/Clinical Findings Patient charts were retrieved from the hospital files for patients who underwent the procedure and were followed for at least 24 months. Five patients (6 eyes) fit the criteria. Cases included Von Hippel’s disease (2 eyes), Coats’ disease (1 eye) and choroidal hemangioma (3 cases). Transscleral diode laser treatment was performed under retrobulbar and topical anesthesia with a retinopexy probe (IRIS DioPexy, IRIS Medical Instruments, Mountain View, CA) applied transsclerally under indirect ophthalmoscope visualization. We found an improvement in best-corrected visual acuity at 24 months postoperatively. Conclusions/Significance Transscleral photocoagulation may have a clinical application in these diseases as an alternate to the high cost of photodynamic therapy with photosensitizing agents.


Introduction
Vascular tumors of the retina and choroid are a major source of long-term visual disability. [1] Contact transscleral photocoagulation with a diode laser is a well-established and relatively safe and effective intervention for glaucoma refractory to management by trabeculectomy or cyclocryocoagulation. Transscleral photocoagulation has been reported in the treatment of diabetic retinopathy, [2,3] retinal breaks, small retinoblastomas, [4] retinopathy of prematurity (ROP), [5,6] and proliferative sickle cell retinopathy [7].
The overall goal was to determine if the novel use of this technique warrants further consideration as a routine therapy for these diseases. We found it to have a potential option as an alternative to photodynamic therapy (PDT) when PDT is unavailable due to its high cost for some patients.

Methods
We conducted a study of the treatment and outcomes of patients with hemangiomatous disease of the retina or choroid and treated with photocoagulation delivered transsclerally under indirect ophthalmoscopic visualization in our facility by the same surgeon (ZM), and followed for at least 24 months. Basic information of the patients is shown in Table 1 including previously medical management, severity of the retinal detachment, treatment parameters, and laser energy with durations and complications.
The records of patients with retinal or choroidal hemangiomas who were treated with transscleral photocoagulation were retrieved from the hospital files. Patient and surgical data were gathered and summarized.
Laser photocoagulation was administered transscleraly with the DioPexy retinopexy probe (IRIS DioPexy, IRIS Medical Instruments, Mountain View, CA, USA) under retrobulbar and topical anesthesia and observed with indirect ophthalmoscopy. An incision was made into the conjunctiva in the quadrant where the lesion was located and the retinopexy probe was inserted through the incision until it contacted the tissue. Laser power was initially set at 300 milliwatts (mW) for 30 milliseconds (ms) and then gradually increased to 1000 to 2000 mW at 2000 ms as needed to achieve tissue ablation. The endpoint of treatment was whitening of the mass. The laser was used to make evenly spaced spots. No patients required a scleral flap.
Obliteration of the mass was confirmed by clinical observation, fluorescein angiography and optical coherence tomography (OCT) at each follow-up. Best-corrected visual acuity was obtained preoperatively and at each follow-up visit ( Table 2). Patients were followed at week 1 and months 1, 3, 6, 12 and 24.
The study was approved by Peking University Third Hospital's Institutional Review Board. Written informed consent was obtained from all participants or their legal guardians before surgery. All data for the current study were analyzed anonymously.

Results
A total of 5 patients (6 eyes) presented with Von Hippel's disease, Coats' disease or choroidal hemangioma. Patients ranged in age from 5 to 53 years.
Case 1 is a 14-year-old female diagnosed with bilateral Von Hippel's disease and a retinal detachment in her right eye. The patient reported gradually decreased visual acuity in her right eye over an 8-month period. Prior to transscleral photocoagulation, she had already undergone bilateral PDT, unilateral argon laser photocoagulation, unilateral intravitreal injection of Avastin (Genentech Inc, California, USA), bilateral cryotherapy procedures and unilateral pars plana vitrectomy for severe vitreous hemorrhage after cryotherapy.
After the written informed consent was obtained from the patient and her parents, transscleral treatment with the diode laser was performed. Laser energy power was delivered at 1400 to 2000 mW for 2000 ms (right eye) and 1000 mW for 1000 ms (left eye).
Fundus examination showed multiple retinal capillary hemangiomas, supplied by large, tortuous afferent and efferent blood vessels, occurred in the peripheral retina in both eyes. Figure 1 shows serum leakage from the hemangiomas and vessels with their extensive retinal exudates with foveal involvement on the right eye at the preoperative fundus examination and their appearance at 2 years postoperatively in the right eye. Figure 2 shows the fundus examination and fluorescein angiography of the localized lesion in the peripheral retina preoperatively and the resolution at 2 years on the left eye. A small vitreous hemorrhage occurred during the procedure ( Table 1). The blood was totally absorbed at 3 weeks postoperatively. Before surgery, the patient's best-corrected visual acuity (BCVA) was finger counting at 10 cm in the right eye and 20/20 Snellen in the left eye. The right eye improved to 20/100 at 3 months and 20/50 at the 6, 12 and 24-month visits. The left eye was 20/20 preoperatively and did not lose any BCVA at any visit ( Table 2).
Case 2 is a 4-year-old male with Coats' disease ( Figure 3). His parents reported that the boy complained of vision loss and he repeatedly covered one eye with his hand. The patient presented with total retinal detachment with extensive exudates. Upon examination, retinal telangiectasia was observed in the temporal superior periphery and a large retinal detachment surrounded by subretinal yellow exudates was observed in the right eye. Fluorescein angiography revealed retinal vascular telangiectasis, areas of capillary distention and nonperfusion, vessel bleeding and light bulb aneurysms characteristic of Coats' disease ( Figure 3, J). No anterior segment abnormalities were noted. This was the first surgical management of this child's disease.
Diode laser photocoagulation was achieved with laser energy power delivered at 1000 to 2000 mW for 2000 ms. The procedure was performed without complications. At follow-up, the large subretinal exudates were almost completely absorbed and the patient had good visual acuity ( Figure 3, Figure 4 and table 2). Before surgery, the patient's BCVA was 20/200. At 1 week, it declined to finger counting at 10 cm and at 6 months it improved to 20/70. At 24 months, BCVA improved to 20/50. Three patients presented with choroidal hemangiomas, vision loss, and hyperopia. Case 3 was a 29-year-old male with a secondary retinal detachment encroaching on the fovea and BCVA of 20/40. Case 4 was a 52-year-old female with serious retinal detachment involving the fovea. Her BCVA at baseline was counting fingers at 10 cm. Both patients had undergone PDT therapy before and suffered of the recurrent of the lesion, but they now sought less expensive treatment. Photocoagulation was Table 1. Basic informations of these patients and clinical outcome.

Discussion
Von Hippel's disease, Coats' disease and choroidal hemangiomas are large vascular abnormalities that are difficult to treat. While many of the current approaches such as cryopexy, transpupillary thermotherapy (TTT) are successful for small  lesions, treatment of massive lesions is more problematic. Damage to the lesion is problematic and recurrence often follows treatment. PDT therapy is a common treatment, but costly and sometimes repeated treatments are required. Many patients cannot afford PDT therapy, especially in developing countries. The diode laser (810 nm) with the characteristic of high scleral transmission and notable absorption, may be an alternative treatment to those large vascular abnormalities. There were reports on treating small retinoblastoma with transscleral laser [4]. According to this study, larger spot sizes and longer pulse durations could be created by the laser modifications. This led the author to use similar treatment parameters to several cases with massive vascular abnormalities which were successfully managed using transscleral diode laser by D-probe with long-duration, large spot size appears complete since the large spots may result in full-thickness chorioretinal necrosis and closure of the overlying retinal vessels [4]. The transscleral diode laser is a long wavelength laser with a good safety profile and fast learning curve in the management of refractory glaucoma. In our cases, visual acuity improved in 5 eyes and remained at 20/20 in the left eye of the patient with bilateral Von Hippel's disease. Vitreous hemorrhage occurred in 1 eye and was reabsorbed without further adverse events. Laser power was initiated at a low level of 300 mW and increased to achieve ablation of the blood vessels.
Coats' disease is a rare idiopathic retinal condition typically found in the first decade of life and results in a gradual loss of vision. Blood leaks from the abnormal vessels and leaving behind cholesterol deposits. Coats' normally progresses slowly. At advanced stages, retinal detachment is likely to occur. Multiple approaches are available for these diseases including observation, laser photocoagulation, cryotherapy, surgical management, and enucleation. Shields et al [8] analyzed 150 Coat's disease patients with different treatment options including observation, cryotherapy, laser photocoagulation, various methods of retinal detachment surgery, and enucleation, and developed a classification system. Patients who present with stage 1 to 3 Coats' disease have the best visual prognosis, and patients with stage 4 or 5 have a poor visual prognosis [8]. Our Coats' disease patient was stage 3b (total retinal detachment). In this classification, the risk for poor visual acuity is 74% in stage 3 in his study [8]. The changes in our Coats' disease patient are dramatic: the previous massive subretinal exudates were almost completely absorbed with good visual acuity by only one time treatment. This successful treatment of this serious stage 3b Coat's disease patient encouraged us to try diode laser prior to vitreous surgery because it is cheaper and easier to perform.
The conventional treatment for Coats' disease involves cryotherapy to ablate abnormal vessels [9,10,11,12]. The outcome of cryopexy for Coats' disease has reported effectively in early cases [9,10,11], however that is less effective in the case with completely retinal detached [10]. Complications of the cryotherapy such as posterior subcapsular cataract and exudative detachment of the retina progressed after treatment are also reported [10]. Experimental test on animals has suggested that there is a significant breakdown of the blood-retinal barrier with both photocoagulation and cryotherapy, but that it is considerably more severe with cryotherapy [12]. Furthermore, patients sometimes require more than one cryopexy procedure to repair the damage and possibly result in thinning of the scleral. Diode laser performed by the transcleral way theoretically has the advantages on both modalities: surgeons can reach the peripheral lesion and performed as cryotherapy with less damages on the blood-retinal barrier as laser photocoagulation.
Laser photocoagulation for Coats' disease has been reported in the literature. Schefler et al used an 810 nm infrared laser to treat patients with stage 3 Coats' disease. [13] In their study, 14 of 17 eyes improved, 2 eyes worsened and 1 eye required enucleation. The difference between their study and ours is the method performed: indirect ophthalmoscopy delivery and 20 diopter lenses. Similar results were reported by Shapiro, using a 532-nm laser for patients with stage 3 Coats' disease; but 3 patients developed cataracts. [14] Three patients developed cataracts. The investigators attributed the cataract development to the laser energy used or the proximity of the laser application to the lens due to the elevation of the retina [14]. We used the 810-nm infrared laser by transcleral contact mode. The surgeon reported that it was easy to target the lesion and the patients were able to cooperate with the surgeon. Cataract was not observed in our study throughout the 2 years follow up. Further studies could be added to tell if the transcleral way is a safe method of laser application. We expect that patients with large vascular lesions When we focused on our choroidal cases, the epiretinal membrane was found in one eye by OCT at 6 months postoperatively. The scar and the epiretinal membrane seemed stable, as was the visual acuity. Careful follow-up is necessary. Surgeons should be great care in treating those lesions adjacent to macular area. If the lesions are not in the center, such as the patient in Case 5 ( Figure 6 and Figure 7), the transcleral diode laser may be as effective as PDT. We did not do a cost analysis, but we theorize that the transcleral diode laser is a more cost-effective approach than PDT treatment.

Limitations
This is a small study in only 6 eyes of 5 patients to explore our current experience with the procedure. Our study was limited to patients who underwent the procedure with the same surgeon and were followed for 2 years, when outcomes would be stabilized. More cases and long term data are needed to establish its efficacy and safety. Our experience in this small study suggests that transscleral photocoagulation may play a role in the treatment of large vascular lesions in retinal and choroidal vascular diseases and is worth further study.
The overall goal was to determine if the novel use of this technique warrants further consideration as a routine therapy for these diseases. We found it to have a potential option as an alternative to PDT when PDT is unavailable.