内窥镜下睫状体光凝术：概述和亚洲视角
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2008年11月10日 15:23:24 Monday
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作者：EShawn Goh, Boon Ang Lim , Leonard Yip 作者单位：1 新加坡陈笃生医院眼科；2 新加坡国立大学杨潞龄医学院眼科
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【摘要】 青光眼手术治疗方法已被分为睫状体破坏性（减少流入）或滤过性（增加流出）两大类。睫状体破坏性手术传统上用于视力预后差的青光眼以及难治性青光眼如外伤后、无晶状体眼、先天性青光眼和发育性青光眼。自从1992年Uram首次使用内窥镜下睫状体光凝术（endoscopic cyclophotocoagulation，ECP）以来，短期和长期的转归已经表明ECP的应用前景广阔。本文在PubMed查询、复习有关ECP的英文文献，并与新加坡一所眼科三级医院的有限结果进行比较。文献报告显示出ECP及联合白内障超声乳化术的ECP在治疗小儿及成人严重的、各种病因所致的青光眼方面的安全性和有效性。这在新加坡某眼科三级医院未发表的短期结果中也有报告，与那些已经发表的结果是一致的。已发表的报告和当前的经验证明，可直视目标组织的ECP，通过内窥镜直视将合适的红外波长激光能量应用于目标组织睫状上皮细胞，避免了“盲目”状态下经巩膜睫状体光凝术所引起的并发症。但是引进这项技术存在着显著的经费困难。ECP在控制眼压和减少抗青光眼药物的依赖性方面是安全有效的。广泛接受和使用这一技术仍有待于大规模的随机对照研究。
【关键词】 青光眼，内窥镜下睫状体光凝术， 睫状体破坏性手术
Endoscopic cyclophotocoagulation: an overview and
Asian perspective
EShawn Goh, Boon Ang Lim , Leonard Yip
1Department of Ophthalmology, Tan Tock Seng Hospital,
Singapore
2Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Correspondence to: EShawn Goh. Department of Ophthalmomlogy, Tan Tock Seng Hospital, 11 Jln Tan Tock Seng Road, Singapore 308433. eshawng@yahoo.co.uk, shawn_goh@ttsh.com.sg
AbstractSurgical treatment of glaucoma has been classified as cyclodestructive (reducing inflow) or filtering (increasing outflow). Cyclodestructive procedures have traditionally been reserved for eyes with poor visual prognoses and refractory glaucomas including posttrauma, aphakia, congenital and developmental glaucoma. Since Uram described the first use of endoscopic cyclophotocoagulation (ECP) in 1992, short and longterm outcomes for ECP have been promising. In the present article, we conduct a Pubmed search and review of published English literature on endoscopic cyclophotocoagulation and comparison with limited results in a single Singapore ophthalmic tertiary hospital. Safety and efficacy of ECP and combined phacoemulsificationECP procedures in treatment of pediatric and adult glaucomas of various etiologies and severities is reported. Local shortterm unpublished results from a single Singapore tertiary ophthalmic service is reported and concurs with previously published results.Published reports and current experience with ECP has demonstrated that ECP with direct visualization of the target tissues avoids the complications associated with blind transscleral cyclophotocoagulation by applying optimum energy to target tissue ciliary epithelium with endoscopic visualization and infrared laser wavelength application. Significant financial barriers exist to introducing this service. It is safe and effective in controlling IOP and reducing reliance on antiglaucoma medications. Widespread acceptance and use of this technique awaits largescale randomized controlled studies.
KEYWORDS: glaucoma; endoscopic cyclophotocoagulation; cyclodestructive procedures
INTRODUCTION
The heterogeneous group of conditions resulting in glaucomatous optic neuropathy have been treated with a combination of medical and surgical therapies. The advent of antiglaucoma medications has reduced the requirement for surgical procedures in glaucoma.
Surgical treatment of glaucoma has traditionally been classified as cyclodestructive (reducing inflow) or filtering (increasing outflow).
Filtering procedures have been the procedure of choice, and in an Asian context are increasingly performed with the use of adjunctive antimetabolites including mitomycinC and 5fluorouracil due to the increased propensity for scarring as well as early and late blebfailure in individuals of pigmented races [1]. Trabeculectomy performed alone or in combination with smallincision cataract surgery is the most commonly performed surgical procedure for glaucoma in Singapore. This is due to its efficacy and relative predictability [1]. However, trabeculectomy surgery is not without its own problems, as it requires frequent postoperative clinic visits and multiple interventions to ensure longterm bleb survivability. In addition, early/late bleb failure and blebrelated complications, ocular hypertension or hypotony, may further complicate the postsurgical course of trabeculectomy [2].
Cyclodestructive procedures have traditionally been reserved for eyes with poor visual prognoses and refractory glaucomas including posttrauma[3,4], aphakia[5], congenital/developmental glaucoma[5,6], and glaucoma associated with previous penetrating keratoplasties [7], as well as eyes with scarred conjunctiva not suitable for filtering procedures [3]. The reticence with the use of cyclodestructive procedures is related to the blind nature of transscleral procedures, and the high incidence of postprocedure inflammation, hypotony, cataract formation and treatment failure [8]. The earliest cyclodestruction methods were performed by surgical excision, diathermy, cryotherapy, light coagulation and eventually laser [4]. Laser cyclophotocoagulation may be performed with an Argon laser through a contact lens via the transpupillary route for aphakic eyes. More commonly, transscleral cyclodestruction is performed through a noncontact or contact probe.
Initial experience using the ruby laser was subsequently superceded by the Neodymium: YttriumAluminiumGarnet (Nd:YAG) laser which demonstrated improved scleral penetration [4]. Further developments in laser technology led to the employment of the compact and portable 810nm wavelength semiconductor diode laser which offers improved melanin absorption and hence selectivity, over the Nd:YAG.
The principles of transscleral cyclophotocoagulation remain identical, regardless of method of delivery. Laser delivery is blind, and requires transmission of laser energy through the sclera, ciliary body and ciliary vessels, before final absorption by the target tissues of ciliary epithelium[9]. Histopathological changes of different modalities of transscleral cyclophotocoagulation are identical, demonstrating moderate to severe disorganization of ciliary processes with fibrosis and atrophy of stroma, as well as nonpigmented and pigmented ciliary epithelium [10,11].
Transscleral cyclophotocoagulation has been demonstrated to be effective for treating severe end stage glaucoma in which other surgeries have failed or potential vision is limited. Within the limitations of varying definitions of success for this procedure, overall success rates vary between 34%81% of patients achieving target intraocular pressure (IOP) with or without concomitant use of antiglaucoma medications, over a mean followup period of 30 months [1215]. This procedure is also associated with a significant incidence of serious complications and postoperative discomfort [15]. In addition, due to the blind nature of treatment delivery, the use of transscleral cyclophotocoagulation is conventionally limited in eyes with disorganized anterior segments.
Uram [4] initially developed and described a novel method to directly photocoagulate the ciliary body under endoscopic guidance, termed endoscopic cyclophotocoagulation (ECP). He was the first to incorporate a diode laser emitting pulsed continuous wave energy at 810nm wavelength, coupled with a 175W xenon light source, heliumneon laser aiming beam and a video camera for imaging whilst recording.
These functions were housed in a 0.88mm (20gauge) probe which offered a 70° field of view (Endo Optiks, ittle Silver, NJ, USA). All elements of the probe are transmitted via fibreoptics. Initial descriptions of the endoprobe were performed in vitreous surgery [16], although the pplications to anterior segment cataract and glaucoma surgery followed.
ECP has been gaining increasing popularity, but concerns still linger about the inherently ablative nature of this therapy, as well as the requirement for intraocular access to perform this procedure.
PERFORMING ECP
Endoscopic cycloablation is performed through an 18gauge (1.2mm diameter probe with viewing angle of 110°) or 20gauge (0.88mm diameter probe with viewing angle of 70°) probe inserted intraocularly. Depth of focus varies from 1mm30mm for the 18 gauge probe, and 0.5mm15mm for the 20gauge probe [3,4]. Laser power (maximum of 1.2W) and duration are adjusted on the console. The actual duration of each treatment is determined by the period of pedal depression.
ECP may be performed in any patients including those of phakic, pseudophakic or aphakes. Due to the requirement for intraocular access in order to perform ECP, this procedure is frequently performed in conjunction with otherintraocular procedures, most commonly with phacoemulsification cataract surgery.
Anterior segment and glaucoma surgeons routinely perform endocycloablation through their choice of preferred clear cornea/scleral tunnel incision. If combined with cataract extraction, the preference is for extracapsular phacoemulsification and posterior chamber lens implantation.
Following placement of the intraocular lens (IOL) into an intracapsular position, the posterior chamber between the posterior surface of the iris and the anterior leaf of the anterior capsule is insufflated with ophthalmic viscoelastic device (OVD). The straight or curved tip endoprobe is oriented outside of the eye, and inserted through the incision and directed toward the posterior chamber. The ciliary processes are photocoagulated under direct visualisation with energy settings commencing between 40mW60mW and adjusted accordingly to achieve shrinkage and whitening of the ciliary processes whilst avoiding an audible “pop” (with bubble formation) indicating excess energy is administered. Energy delivered is minimized to avoid significant breakdown of the bloodaqueous barrier and excessive inflammation. Initial photocoagulation is directed at the raised processes without affecting the “valleys” of nondisplaced ciliary epithelium. A minimum of 270° to a maximum of 360° is treated. A single incision is adequate to perform 180° of photocoagulation with a straight probe, whilst a similar incision is adequate to perform treatment over 270° for a curved probe. At the conclusion of the procedure, remaining OVD is removed from the anterior chamber by irrigation with balanced salt solution, and the wound is closed in the usual manner.
A posterior approach may be indicated in certain clinical conditions including aphakia or severe posterior synechiae limiting ciliary sulcus access. This is performed via standard 3port pars plana vitrectomy with limited anterior vitrectomy. This would allow safe and adequate access to all ciliary processes. Treatment parameters and end points are identical to the anterior segment approach. Wound closure is in the usual manner for posterior segment surgery.
At the conclusion of surgery, an appropriate antiinflammatory and antibiotic regime is administered as per routine cataract surgery. Cycloplegics, nonsteroidal antiinflammatory drugs (NSAID) and routineglaucoma medications are administered. The exceptions include miotics and prostaglandin analogues which may theoretically exacerbate intraocular inflammation and its attendant sequelae. Oral acetazolamide is administered postprocedure in patients with advanced glaucomatous damage for prophylaxis against intraocular pressure spikes due to inflammation, or retained OVD. Glaucoma medications are expected to be continued for 24 weeks until the clinical effects of ECP suggest tapering of glaucoma medications are appropriate. Hollander and Lin [7] described an isolated case of delayedECP effect 3 months following treatment for penetrating keratoplastyassociated ocular hypertension. This suggests that delaying ECP retreatments in medically controlled glaucoma for patients with good visual potential may result in late treatment benefit, whilst offering the benefit of avoiding overtreatment. Topical antibiotics are administered for a minimum of 1 week, whilst steroids, NSAIDS and cycloplegics are tapered as inflammation subsides. Glaucoma medications are removed as clinically dictated.
CLINICAL RESULTS OF ECP
Clinical experience with ECP has been expanding rapidly. Literature review was performed using a Pubmed search with the key words “endoscopic” and “cyclophotocoagulation” This returned a total of 15 published reports in the English language, between the years 1992 and 2007.
The first description of ECP was reported by Uram [4] in 1992. The initial reports for ECP included a retrospective case series of 10 eyes with recalcitrant neovascular glaucoma treated with ECP for treatment areas of between 90180°. After a mean followup of 8.8 months, the eyes demonstrated a mean reduction of 28.3% and a significant reduction in requirement for systemic and topical antiglaucoma medications. Subsequently, Uram described a larger case series of 143 patients with intractable neovascular glaucoma, which demonstrated a dramatic IOP reduction of 67.6% from baseline, with a similar reduction in requirement for systemic and topical antiglaucoma medications. There were no reports of serious intraoperative complications.
Following these initial descriptions of ECP, subsequent studies evaluated the safety and efficacy of ECP in the treatment of other forms of refractory glaucomas [3,5,9,1720]. The majority of studies described retrospective case series or poorly designed prospective studies. There was a predominant problem of the lack of a uniform definition for success which makes comparison between studies difficult.
Several reports retrospectively describe case series of ECP in the treatment of recalcitrant glaucomas [3,18]. Uram [4] was the first to describe the effects of phacoECP against phacoemulsification alone. Chen et al [19] reported their series of 68 patients with diverse forms of refractory glaucoma which had failed prior treatment on maximal medical therapy and previous filtration/cyclodestructive procedures. Mean IOP reduction of 34% was reported after an average followup period of 12.9 months, with a corresponding decrease in requirement for antiglaucoma medications. No significant intraoperative complications were described, with the exception of postoperative inflammation, transient choroidal detachment and a single case ofmalignant glaucoma.
Berke [21] was the first to report a randomized series of sufficiently large cohort and length of followup comparing combined phacoECP patients gainst phacoemulsification alone. He reported a series of 626 eyes with mean followup of 30 months of patients with moderately severe glaucoma. He compared in a randomized, nonblinded fashion patients treated by five surgeons with combined phacoECP against phacoemulsification alone. Treatment endpoints included mean IOP reduction and mean reduction in antiglaucoma medications. With regards to the primary endpoints, there was no statistically significant difference for the phacoemulsification group alone, whilst the combined phacoECP group demonstrated mean reduction of IOP from 19.13±4.14 to 15.73±3.00mmHg (P<4.48×1072), and reduction in mean number of antiglaucoma medications from 1.53±0.89 to 0.65±0.95 (P<1.23×1085). Berke [21] concluded that phacoECP effectively lowered IOP as well as reduced the number of antiglaucoma medications required after 2 years, which translated into effective costsavings for the patient and the medical community. Combined phacoECP did not increase the potential for developing cystoid macular edema postoperatively, not was it associated with an increased risk of serious complications such as endophthalmitis and visual loss compared to phacoemulsification alone. Rates of cystoid macular edema were slightly lower in the combined phacoECP group (0.8% vs 1.2%) compared to the phacoemulsification group alone, although this difference was not statistically significant.
Gayton [22] published the only randomized controlled trial to date comparing combined cataractglaucoma surgery (phacotrabeculectomy) versus cataractECP. In his study, 58 eyes in 58 patients with combined cataract and progressive glaucoma requiring surgery were randomized into treatment arms of combined phacotrabeculectomy versus phacoECP. These patients were followed up for 2 years and the main outcomes measured were postoperative inflammation and intraocular pressure (IOP). Treatment failure was defined as IOP control requiring subsequent surgical intervention.
Study results showed that IOP reduction was greater immediately postoperatively in the trabeculectomy group, but both groups were equivalent at 1 month followup. In the immediate postoperative period, less inflammation was observed in the ECP group. In general, however, the overall IOP reduction was greater in the trabeculectomy group, and less antiglaucoma medications were required at all time points during followup. Trabeculectomy patients achieved target IOP control without medications in 42% of cases, compared to 30% for ECP patients. For patients achieving IOP control with medications, this was 54% for trabeculectomy vs. 65% for the ECP group. Overall success rates for IOP control with or without medications were identical. Most significantly, there were no cases of posttreatment hypotony in either group. ECP was demonstrated to be effective in reducing IOP, was less invasive, caused less inflammation and has potentially less complications than traditional trabeculectomy filters.
Lima et al [17]. described 34 patients in a prospective series comparing refractory pseudophakic glaucoma versus Ahmed tube implantation. Similar to previous studies, the ECP patients demonstrated significant reductions of 66.2% (average of 27.54mmHg) and mean reduction of one antiglaucoma medication after a mean followup of 21.29 months. The ECP group reported an overall higher success rate of 73.53% (IOP<21mmHg) with or without antiglaucoma medications. Most importantly, there were no serious complications associated with ECP, were simpler and less timeconsuming to perform than Ahmed tube implantation.
ECP efficacy in treatment of pediatric glaucomas has also been demonstrated in several retrospective case series. Neely et al [5，6，23] treated 36 eyes of 29 patients with childhood glaucomas of differing etiologies. Treatment strategy varied between 180° and 270° (mean of 260°). Mean followup period of 19 months demonstrated that 34% eyes were successfully treated with a single treatment (mean reduction of 30%), and 43% achieved target IOPs with >1 treatments (average of 1.42 procedures). The most significant complications occurred in four aphakic eyes which included two eyes with retinal detachments, one eye with chronic hypotony and one experiencing severe visual loss (hand movement vision deteriorating to no perception of light). Neely concluded that ECP was moderately effective for the management of difficult pediatric glaucomas, with aphakic patients having an increased risk of significant postoperative complications. Table 1Endoscopic cyclophotocoagulation: an overview and Asian perspective YearAuthorAge（略）
Published Asian experience has been limited, with initial results trending towards general agreement with previously published results in Caucasian populations. Yip et al reported unpublished early results of 23 eyes in 22 patients treated with ECP in a single tertiary centre in Singapore between October 2004 and April 2005. Eighteen eyes had combined phacoemulsificationECP for moderate to severe glaucoma of various etiologies. They reported overall success rates of 78.3% of eyes achieving target IOP of 22mmHg or lower with or without antiglaucoma medications. There was a mean reduction in IOP (from 20.96±4.63mmHg to 17.83±6.19mmHg) which was statistically significant (P=0.003) and number of antiglaucoma medications required from 2.0±0.8 to 1.0±1.1. Both treatment endpoints demonstrated statistical significance (P=0.003). No serious postoperative sideeffects were observed, however three (13%) patients reported moderate visual loss (VA loss >10 ETDRS letters).
CONCLUSION
Published reports and current experience with ECP has demonstrated that this novel technique of treatment delivery with direct visualization of the target tissues avoids the complications associated with blind transscleral cyclophotocoagulation by applying optimum energy to target tissue ciliary epithelium with endoscopic visualization and infrared laser wavelength application. Table 1 summarises the major studies in the English language examining the safety and efficacy of ECP in the management of moderate to severe glaucomas in eyes with good to poor visual prognoses. Across all etiologies, disease severity and agegroups, ECP has been demonstrated either in isolation or performed in combination with phacoemulsification, to effectively lower IOP in a sustained fashion and reduce the number of antiglaucoma medications required to achieve target IOP in a costeffective manner. Literature review in the previous 15 years suggests that the total reported shortterm complication rates are less than 25% for severe inflammation, cataract or hyphema formation, and longterm complication rate of reduced vision for any reason is <16% in any individual study related to ECP treatment. Overall review of reported numbers for all glaucoma types and severities treated with ECP, suggest that the longterm complication rate is less than 4.6%.
The use of ECP has had strong support in certain sections of the ophthalmic community in which glaucoma management is a significant part of their practice. Its relatively lowrate of takeup in the majority of centres, especially in most parts of Asia include the prohibitive startup costs of ECP equipment versus traditional filtering surgery equipment. As a surgical adjunct, ECP widens the choices available to glaucoma specialists in managing refracatory glaucomas, particularly in clinical situations with limited visibility of the anterior segment or failed transscleral endocyclophotocoagulation. It has demonstrated safety and efficacy in retrospective and small randomized trials in controlling IOP for all etiologies of glaucoma, reducing dependence on antiglaucoma medications, as well as delaying progression to filtering trabeculectomy shunt procedures.
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