Individualized transscleral cyclophotocoagulation as the initial surgical intervention for medically uncontrolled glaucoma after blunt trauma

Aim: To investigate the safety and feasibility of individualized transscleral cyclophotocoagulation (TSCPC) as the initial non-incisional surgical intervention for medically uncontrolled glaucoma after blunt trauma. Methods: The therapy records were reviewed of medically uncontrolled traumatic glaucoma after blunt trauma treated with TSCPC in a single hospital between January 2014 and December 2018. Thirty-one patients (31 eyes) received individualized TSCPC after ultrasound biomicroscopy and gonioscopy examination to localize and quantify the injured quadrants of the anterior chamber angle. In addition to the number of IOP lowing drugs, visual acuity (VA), IOP, inflammation and hemorrhage in the anterior chamber were analyzed at 1 day, 3 weeks and 3 months after operation, respectively. Success was defined as the IOP was not more than 21 mmHg. Results: Compared with the data of pre-operation, constituent ratio of VA had no significant difference at 3 weeks (χ2 = 0.56, p > 0.75). At 3 months the average IOP was 22.2 ± 6.8 mmHg, which was significantly lower than that of pre-operation (46.6 ± 5.6 mmHg) (t = 19.818, p < 0.001). No IOP lowing drug was needed in 12 eyes, and more than three kinds of drugs were still needed in five eyes. The average number of medications decreased to 1.2 ± 1.2 (χ2 = 93.496, p < 0.001). The complete success rate was 38.7% and the relative success rate (combined with no more than two kinds of drugs) was 83.9% at 3 months. Conclusions: Individualized TSCPC could be applied as an initial non-incisional surgical intervention to treat traumatic glaucoma refractory to the medicine therapy.


Introduction
The patients of ocular trauma in China were estimated to be about 5 million to 12 million per year. 1 Closed globe injury accounted for about one-third of patients hospitalized for ocular trauma. 2,3 Ocular contusion was the main type of closed globe injury, which was often accompanied by high intraocular pressure (IOP). If IOP could not be controlled quickly and effectively, optic atrophy would lead to blindness. Traumatic angle recession, inflammation, intraocular hemorrhage and lens-related factors were the most important pathogenesis of secondary glaucoma after blunt trauma. 4,5 Topical and systemic IOP lowering drugs were the common initial medical treatment. Targeting at the main factors leading to elevated IOP, timely operation to remove severe intraocular hemorrhage, lens subluxation and vitreous hernia was suitable strategy. 6 If these surgical indications were not available, close clinical observation and selective surgical repair of the intraocular injury when the condition was stable could be a reasonable choice. However, the IOP of some cases might be beyond control with the maximum tolerated medications. Early anti-glaucoma surgery would be inevitable.
Routine surgical intervention for medically uncontrolled glaucoma was trabeculectomy or tube implantation. However, postoperative scarring is one of the factors associated with surgical failure, especially among the traumatic glaucoma patients. The outcome may be even worse when incisional surgery is carried out in the state of uncontrolled IOP, because of activated inflammatory reactions and possible bleeding crisis. As we know, cyclophotocoagulation was often performed only as the secondary or even the last option. Recently, successful outcomes of refractive glaucoma treated by transscleral cyclophotocoagulation (TSCPC) had ever been reported. 7-9 So we selected TSCPC as the initial non-incisional surgical intervention for medically uncontrolled glaucoma cases, whose IOP was higher than 35 mmHg treated with the maximum tolerated dose. In the study individualized TSCPC was applied based on a careful evaluation of elevated IOP and the severity of the anterior chamber angle injury by ultrasound biomicroscopy (UBM) and gonioscopy examination, the safety and feasibility of the operation were evaluated for 3 months.

Patients
Retrospective analysis was performed on medical documents of the traumatic glaucoma patients after ocular contusion treated with individualized TSCPC in our hospital from January 2014 to December 2018. Diagnostic criteria of traumatic glaucoma after ocular contusion: pathological elevation of IOP because of closed globe injury, which would lead to glaucomatous optic neuropathy and need to be controlled with anti-glaucoma medications or operation. The inclusion and exclusion criteria for patients in the study was as following.

Methods
The recruited patients signed informed consent before operation and the study was approved by the ethical and academic board of Xijing Hospital. All procedures used conformed to the tenets of the Declaration of Helsinki. Information including gender, age, occupation, injury date and source, tissues involved, best corrected vision acuity (BCVA) and IOP were filled according to the forms of World Eye Injury Registry. All TSCPC procedures were performed by one surgeon.
The number of the quadrant to be treated was determined by the accumulated injured angle range. If angle recession exceeded 180°, 3 quadrants would be treated. Otherwise 2 quadrants were chosen. During laser delivery, 25-40 burns were distributed evenly at the discretion of the clinician depending on the level of IOP (35-40 burns for the patients with IOP >40 mmHg) and the number of injured quadrant to be treated (25-30 burns for 2 quadrants, 30-40 burns for 3 quadrants). In detail, after localization and quantification of the injured quadrants of the globe by UBM and gonioscopy examination, 2 or 3 quadrants covered the injured angle were selected to perform TSCPC with diode laser (Iridex Corporation, Mountain View, CA, USA) under retrobulbar anaesthesia with ropivacaine 1% and lidocaine 2% mix (1: 3). During laser delivery, the probe was placed 1.5 mm posterior to the corneal limbus avoiding the 3 and 9 o'clock positions. The initial laser energy setting was 2000 mW and the treatment duration was 2000 ms. If the 'pop' sound was inaudible, the energy setting was increased by 250 mW and the maximum power of the diode laser did not exceed 3000 mW. Subconjunctival injection of dexamethasone 0.2 mg was given afterwards. Topical bromfenac sodium and prednisolone acetate eye drops were applied for 4 to 6 weeks after operation.
The BCVA, IOP, inflammation and haemorrhage in the anterior chamber, glaucoma medications were observed after operation for 1 day, 3 weeks and 3 months. The complete success was defined as: The IOP was less than 22 mmHg without glaucoma medications. The relative success was defined as: The IOP was less than 22 mmHg combined with no more than two anti-glaucoma medications. The order of combined medication was beta-blockers, alpha agonists, carbonic anhydrase inhibitors and prostaglandin analogues. Patients needing vitreous or cataract surgery due to injury progression during the follow-up were removed. The definition of failure at 3 months included: IOP was over 21 mmHg combined with three or more anti-glaucoma medications; further anti-glaucoma surgery was needed; loss of vision; hypotony (under 7 mmHg) or eyeball atrophy.

Statistical analysis
Data analysis was performed with SPSS software, version 19.0 (SPSS Inc, Chicago, IL, USA). Continuous variables were presented as mean ± standard deviation. Classified data were presented as the number (n) and percentage (%). The paired t-test was used for comparison of the level of IOP between pre-operation and post-operation at different time points. Both the constituent ratio of BCVA and the average number of medications before and after operation were analyzed by the chi-square test. Statistical significance was considered at p < 0.05.

Baseline characteristics
A total of 31 patients (31 eyes) were included. There were 28 males (90.3%) and 3 females (9.7%). The average age was 36.6 ± 11.9 years (19-66 years). Age groups were recommended by the Chinese Society of Ocular Trauma: 4 cases were 18 to 24 years old (12.9%), 25 cases were 25 to 55 years old (80.6%) and 2 cases were over 55 years (6.5%). The young and middle-aged were the main population of ocular contusion. Injury source and place included fist, fireworks, motor vehicle crash, recreation and sport, industrial premises and home ( Table 1). The main ocular injuries of these patients included hemorrhage in the anterior chamber and vitreous, anterior angle recession, iridodialysis and lens subluxation.
Parameters of laser settings for each patients were shown in Table 2. For the 31 patients recruited, the average degrees of angle injury was 284.5° ± 69.2° (150°-360°), the average laser power was 2500 ± 273.9 mW (2000-3000 mW), and the average number of burns was 33.7 ± 4.6 (25-40). Twenty-seven patients were treated with TSCPC in 3 quadrants of the globe. Four patients were treated on 2 quadrants since the accumulated injuried angle was not more than 180°. The injured quadrants confirmed by UBM and gonioscopy examination was selected as the location for treatment.

Best corrected visual acuity
The BCVA was graded according to the International Society of Ocular Trauma as NLP, LP/HM, 0.005 to 0.095, 0.1 to 0.3. The constituent ratio of BCVA after injury and 3 weeks after treatment was shown in Figure 1. There was no significant difference in constituent ratio of BCVA by chi-square test (χ 2 = 0.56, p > 0.75), indicating TSCPC was a safe option in treating refractive traumatic glaucoma.

IOP and the success rate
The IOP was significantly reduced on the first day after surgery. At 3 weeks, the IOP of 17 patients were under 22 mmHg without medications. At 3 months, the average IOP was 22.2 ± 6.8 mmHg. The IOP of 12 patients were under 22 mmHg without medications, at least three kinds of drugs were needed in five cases ( Table 2). Paired t-test showed that the IOP was significantly lower at all time points after the operation than that before operation (p < 0.001). The average number of medications was 1.2 ± 1.2 and reduced obviously after operation by the chi-square test (χ 2 = 93.496, p < 0.001). The complete success rate was 38.7% and the relative success rate (combined with no more than two kinds of drugs) was 83.9% at 3 months (Table 3).

Complications and surgery failure
On the first day after operation, mild to moderate bulbar conjunctival hyperemia and chemosis occurred. A small amount of dusty and pigmented keratic precipitates could be seen on the posterior surface of the cornea. Moderate flare and inflammatory cells were present in the anterior chamber, and hemorrhagic aqueous humor could be seen in some cases. However, there was no massive hyphema increased in the anterior chamber compared with that before operation. At 3 weeks, chemosis disappeared with or without mild congestion, and there were few inflammatory cells in the anterior chamber. One patient received the second TSCPC after 3 months because of re-elevated IOP. The IOP of two patients were lower than 7 mmHg after surgery because of higher laser power setting and number of burns delivery, and recovered within a week after treatment ( Table 2). During the 3 months of follow-up the patients showed no persistent hypotony or eyeball atrophy.
When dealing with uncontrolled IOP induced by trauma, higher risk and incidence of complications often made both ophthalmologists and patients uneasy to make the decision for surgery. Incisional surgical intervention like trabeculectomy and drainage implantation was a kind of option. Ahmed or Baerveldt tube shunt provided successful control of IOP in patients with medically uncontrollable traumatic glaucoma in several small sample observations. However, hypotony, shallow anterior chamber, hyphema, tube extrusion might fail the surgery. 13,14 In addition, complications of incisional surgery in the early stage might include: moderate to severe inflammation, intraocular hemorrhage, IOP fluctuation followed by aggravation of lens displacement and vitreous hernia, earlier scarring and vascularization of the filtering bleb. Traumatic glaucoma was often complicated with other intraocular injuries, which could increase the complexity of treatment. So when choosing incisional surgery, the issues like incision position, bleb location, combined surgery or not, and the surgical impact on the future treatment should all be taken into account. For instance, the inferotemporal quadrant should be selected as the best operative approach when the drainage valve was inserted for the glaucoma patients who would need vitrectomy combined with silicone oil filling in the later stage. 15 As an non-incisional surgical intervention, TSCPC had been applied to treat acute angle closure refractory to medical treatment safely and effectively. 16,17 Additionally, a study of secondary glaucoma in children after ocular trauma and cataract surgery found that TSCPC had a similar effect on controlling IOP and maintaining visual function as trabeculectomy. Meanwhile, the incidence of complications of TSCPC was lower, while the success rate of trabeculectomy depended more on the convenience of follow-up and postoperative care. 18 Another study showed a substantial and long-term reduction of IOP in glaucoma patients following TSCPC. 19 Glaucoma patients with good VA could also be treated with TSCPC safely and effectively in controlling IOP. The loss of VA in some patients was similar to the patients having trabeculectomy or tube surgery. 20,21 Blunt force trauma would likely affect more than just the area of angle recession. Besides the above factor, in the clinic it is hard to weigh the injury of angle accurately and visually. Sometimes marginal changes in laser power delivery may jeopardize a complete success and lead to the risk of loss of vision and hypotony. In this study, we quantified the quadrant with angle recession, which was relatively easier to conduct and personalize. Meanwhile, the power of laser and the number of burns were set at the discretion of the clinician during laser delivery to achieve a better and safe outcome. TSCPC had its own advantages, including a simpler procedure, less postoperative care and follow-up, lower cost and notable effect. So it was suitable for the patients who might not qualify for trabeculectomy or tube implantation. In our study individualized TSCPC was applied as the initial non-incisional surgical intervention for traumatic glaucoma patients with visual potential. The injured quadrants of the anterior chamber angle was confirmed by UBM and gonioscopy examination before personalized treatment parameter was set. The relative success rate (combined with no more than two kinds of drugs) was 83.9% at 3 months which was comparable as the previous study. The BCVA was stable at 3 weeks. Data of BCVA at 3 months were not analyzed because the complicated factors related to trauma itself might result in cataract development or atrophy of the optic nerve leading to vision loss. After 3 months, some patients underwent cataract extraction, vitectomy or intravitreal injection due to the progression of traumatic cataract, macular hole or choroidal neovascularization. So the data quality and consistency were not good for analysis then. The most common complication was postoperative iritis. Hyphema was rare, and a little bleeding or hemorrhagic aqueous humor could be absorbed within 1 week generally. Only one patient received the second TSCPC after 3 months because of uncontrolled IOP once more. The IOP of two patients were lower than 7 mmHg related to higher energy settings and the low secretion of the shocked ciliary body, who both recovered with the treatment of anti-inflammation and paralysis of the ciliary muscle.
Over the past several decades, cyclodestructive techniques like cyclodiathermy and cyclocryotherapy had been reserved as the final options for refractory glaucoma because of the complications including pain, hyphema, vision loss, hypotony and phthisis. 22 With the development of technology, innovations of micropulse transscleral cyclophotocoagulation and high-intensity focused ultrasound was available in clinic. Lower damage, minimal invasion and fewer complications made the interpretive term 'destructive' out of date and improper. New encouraging clinical results cast a broad view in the application of this kind of surgery as primary treatment for refractory glaucoma. [23][24][25] In this study TSCPC treatment created conditions and foundations for other ocular trauma-related complications that might need to be dealt with and visual function rehabilitation at a later stage.
This single center retrospective study might bias because of the small sample and the inconsistency of medication schemes. In order to evaluate clinical therapeutic value of TSCPC for these patients, we advocated to carry out a multi-center study on the treatment of medically uncontrolled glaucoma after blunt trauma with individualized TSCPC as a preferred procedure in the future. It would be very meaningful to investigate whether the outcome of the BCVA could be improved if the time point of the operation was a few more days in advance.

Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.