Laser Transmission and Absorption
The choice of laser type for transscleral cyclophotocoagulation (CPC)has been based on scleral transmission rather than on efficacy at the target tissue. Since scleral transmission increases at longer wavelengths, the lasers most frequently employed in clinical practicehave been the 810nm diode and the 1,064nm neodynium: yttrium–aluminium–garnet (Nd:YAG). However, the contact application with pressure on the sclera increases scleral transmission, especiallyat shorter wavelengths.1 This increase is 2.5-fold for the krypton laser compared with 1.5-fold for the Nd:YAG laser. Moreover, the wavelength of red 647nm krypton and 670nm diode lasers is near to that maximally absorbed by melanin granules (600nm) in the retinal pigment epithelium. Melanin granules absorb 670nm laser twice as effectively as 810nm diode laser and six times more effectively than 1,064nm Nd:YAG laser.2 Lesions in the pars plicata of the rabbit eye, similar to those obtained using contact Nd:YAG lasers, can be produced by red lasers using only half the energy.3 The poorer scleral transmission and better absorption by melanin of the red lasers indicate that less energy enters the eye, the vitreous humour and the retina of the contralateral wall of the eye, which may be of practical importance.
Possible Cellular Effects and Mechanisms of Intraocular Pressure Reduction
The low power (0.4W) and the long duration of application (10 seconds) may result in parts of the ciliary body lesions being warmed to levels above 43°C but not being coagulated. Such hyperthermic effects may induce apoptosis in the cellular components of the ciliary body4 instead of necrosis, which occurs after coagulative lesions. It is known that, compared with necrotic cell death, the inflammatory reaction following apoptosis is minimal.4,5 The hyperthermia produced in the lesions by the lowpower, slow-burn laser may partly explain the mild post-operative uveitis observed after this treatment modality.6–13
The mechanism of intraocular pressure (IOP) reduction after CPC has been debated. In addition to destroying the epithelium and capillaries of the ciliary processes,14 the findings support the view that non-conventional outflow routes, including uveoscleral outflow, are increased after CPC.7,15
Morphological Changes After Red Laser Cyclophotocoagulation
A histopathological study of an eye after long-term successful krypton laser CPC showed that effective ablation of the ciliary processes was achieved and only a slight chronic inflammatory reaction was present. Also, the sclera, iris, lens and zonules were intact.7 The histological changes observed after 670nm diode laser CPC are essentially identical.8 With the use of in vivo confocal microscopy, no changes were noted in the corneal layers or subbasal nerves after krypton laser CPC. In addition, corneal sensitivity, tested with the Cochet-Bonnet esthesiometer, was normal, as was tear fluid secretion.16
Cyclophotocoagulation in the Treatment of Therapy-resistant Inflammatory Glaucoma
There are only a few reports on the treatment of inflammatory glaucoma with contact transscleral CPC.17–22 In most studies 810nm diode lasers were used; in only one study were red 647nm krypton and 670nm diode lasers used.9
Red Laser Cyclophotocoagulation in the Treatment of Therapy-resistant Inflammatory Glaucoma Patients
We retrospectively reviewed the charts of 38 consecutive patients (25 adults, mean age 50.4±13.3 years, and 13 children, mean age 10.8±3.1 years) treated with the 647nm krypton or 670nm diode laser for therapy-resistant inflammatory glaucoma at Helsinki University Eye Hospital from December 1991 to March 2004.9 Two patients were excluded (one with chronic uveitis and retinal ablation and another with chronic uveitis and neovascular glaucoma). Follow-up data were retrieved from the patient files of Helsinki University Eye Hospital and of the referring centres. The follow-up was 42.8±40.0 (range two to 145) months. The main underlying inflammatory disease was chronic uveitis (31 out of 34 adult eyes and 14 out of 14 children’s eyes), but one adult eye had scleritis and two adult eyes had scleritis with keratouveitis. Maximal tolerated medication had been given. Nineteen of the 48 eyes had failed glaucoma surgery (trabeculectomy, cyclocryocoagulation, implant surgery): 16 of 34 adult eyes (47%) and three of 14 children’s eyes (21%). Also, other modes of surgery had been performed (see Table 1).
Methods
The CPC was performed under periocular anaesthesia in adults; children were treated under general anaesthesia. With the patient in a supine position, the pars plicata region of the ciliary body was identified using transscleral illumination. The 647nm krypton laser was delivered from a Lasertek 41 AKTrKr krypton laser unit, and the 670nm diode laser from a prototype 670nm diode laser unit (Dual Laser Oy, Helsinki, Finland) via a fibre optic tip (Laser Peripherals, Inc., Minnetonka, MN, US/Dual Laser Oy, Helsinki, Finland). At the tip of the probe, the power was 0.35–0.5W in the krypton group and 0.40–0.45W in the 670nm diode group (Scientec Calorimeter, Bolden, CO, US). The probe was held perpendicular to the scleral surface and pressed at the site of the pars plicata shadow. Each application lasted for 10 seconds. At the first session the inferior 180º of the ciliary body was treated. If needed, a second treatment was given to the temporal 180º, a third treatment to the inferior nasal 90º and superior temporal 90º and a fourth again to theinferior 180º. One quadrant was always left intact in an attempt to avoid hypotonia. To avoid post-operative IOP rises, a drop of 1% apraclonidine or 250mg oral acetazolamide, or both, was given before treatment. After treatment, the patients used antibiotic steroid drops four to five times a day for three to four weeks. Previous antiglaucoma and/or anti-inflammatory medication was continued, but with the follow-up it was tapered off according to the therapeutic response.
Statistical Methods
Pre- and post-operative IOP levels and pre- and post-operative glaucoma medications were compared using the Wilcoxon signed rank test. The non-parametric Quantile (Sign) test was used to compare pre- and post-operative visual acuity. p<0.05 denoted statistical significance of differences. Missing data were notsubstituted by any method.
Results
Treatment was defined as a success if IOP was reduced to 6–21mmHg with or without medication. After one or repeated CPCs, the mean IOP of the adults fell from a baseline of 36.4±8.9mmHg to 16.4±7.2mmHg at the last follow-up; among children the corresponding figures were 33.8±5.5 and 22.0±9.6mmHg, respectively (see Table 2). At the last follow-up, after one or more CPCs but no other glaucoma procedures, an IOP of 6–21mmHg was achieved in 85.3% of the adult eyes. Among children, 92.3% were successes at one month, but then the effect started to taper off. After two years only 14.3% were still controlledaccording to our criteria. Fifty-nine per cent of the adult eyes and 36% of the children’s eyes needed a repeat treatment: 31% were treated twice, 31% three times, 6% four times and 2% five times. At the end-point, 23% of the adult eyes and 43% of the children’s eyes needed incisional glaucoma surgery combined with a topical antimetabolite or a shunt.
After treatment, 73% of the adults could be maintained with topical glaucoma medication only. Pre-operatively, 68% of the adults were on oral carbonic anhydrase inhibitors (CAIs), but only 36% needed them post-operatively. Among children, similar alterations in glaucoma medication were not noted: 23% used oral CAIs both pre- and postoperatively. The baseline visual acuity was not reduced after CPC (see Table 3). Decline in visual acuity of >2 Snellen lines was noted in 5 eyes, but nine eyes showed improvement of >2 Snellen lines – five after cataract operation, one after laser capsulotomy and three for some other reason. The main causes of the decline of visual acuity were progression of cataract or development of cystic macular oedema (CME) due to uveitis (see Table 4). No ‘pop’ effects were noted. Marked ciliary injection occurred seldom and no cases of persistent hypotonia or phthisis were seen (see Table 5).
Comparison of Red Laser with 810nm Laser Cyclophotocoagulation in Inflammatory Glaucoma
With red lasers the power at the scleral surface is only 0.35–0.45W, whereas with the 810nm diode laser it is 1.5–2W. With the red lasers the duration of each application is 10 seconds, whereas with the 810nm diode laser it is 1.5–2 seconds. Red lasers allow a slow release of low-dose, short-wavelength laser energy and may thus induce less trauma to the eye, which explains the low rate of complications. No explosive pop effects, severe anterior uveitis or hypotonia were encountered in our study. Also, visual acuity remained close to the pre-operative level.9
In a prospective study by Schlote et al.,21 18 eyes with chronic uveitis/trabeculitis were treated with transscleral 810nm diode laser CPC. Their success rate of 72% is very similar to that seen in our study. Also, the figure of 63% needing more than one treatment corresponds well to our figure of 56%. No serious complications occurred in their study. Nearly half of the patients had mild anterior uveitis on the first post-operative day, and no marked activation of the underlying inflammatory disease was seen. In two eyes pop effects during the operation were encountered, and conjunctival burn in one. Visual acuity decreased in 38%.
In a retrospective study by Heinz et al.,19 21 eyes of 12 paediatric patients with juvenile idiopathic arthritis (JIA)-associated uveitis and secondary glaucoma were treated with transscleral 810nm diode CPC as a primary surgical treatment. An IOP ≤21mmHg was achieved in only 32% of the eyes. Pop effects occurred in six of 41 treatments (14.6%) and a change in pupil configuration in four eyes (21%). No hypotonia or severe increase in inflammatory activity was seen in their study.
In the study by Bloom et al.,17 210 eyes of heterogenous glaucoma patients were treated using 810nm diode laser CPC. Nine eyes with inflammatory glaucoma were included. In eyes with inflammatory glaucoma, IOP fell from a pre-operative level of 33.3mmHg to 18.0mmHg at the last follow-up. No phthisis or hypotonia occurred in these eyes, but macular pucker was seen in one eye. In contrast, in the study by Murphy et al.20 16 out of 263 eyes had uveitic glaucoma. Maximum hypotonia and phthisis occurred in 18.8 and 12.5% of eyes with uveitic glaucoma, respectively, after treatment with 810nm diode CPC. In eyes with uveitic glaucoma the success rate was high (75%) and the re-treatment rate was low (38%). The authors suggested reduction of laser energy – in particular in patients with high pre-operative IOP, and especially if associated with neovascular or uveitic glaucoma – to limit the hypotonia rate.
Conclusion
Low-dose energy with slow release is equally effective as the 810nm diode laser with higher energy pulses delivered in 1.5–2 seconds. The absence of severe side effects and post-operative pain makes this simple outpatient procedure a useful alternative in the management of treatment-resistant inflammatory glaucoma in adults before incisional surgery with shunts or antimetabolites is considered.
