Incisional Surgery as the Initial Treatment of Open-angle Glaucoma

Until recently considered a late-stage option, trabeculectomy may have a place in early glaucoma treatment.

By Henry D. Jampel, MD, MHS

The use of eye drops to lower intraocular pressure is far from a perfect solution for our glaucoma patients. Even under ideal circumstances, such as those encountered in rigorous clinical trials, medication can only reduce the risk of an ocular hypertensive developing glaucoma by about 50%,¹ and in established glaucoma only reduces the proportion of patients getting worse by about 25%.² In real-world circumstances, in which adherence to a chronic regimen is often poor,³ and where even those patients who do attempt to instill their eye drops often fail technically,⁴ the effect of prescribing eye drops is likely to have even a smaller effect in preventing vision loss from glaucoma. Couple this insufficient IOP control with local and systemic side effects and it is no wonder that physicians have sought a surgical fix for glaucoma. Could trabeculectomy be that fix? Let's take a look at recent research for an answer.

First Explorations

The concept of initial surgery for glaucoma was first tested in the United Kingdom in the 1980s, first by Jay⁵ and then Roger Hitchings and his group at Moorfields Eye Hospital.⁶ The latter group performed a randomized clinical trial in which patients with newly diagnosed open-angle glaucoma were randomized to topical therapy, laser trabeculoplasty or trabeculectomy. Note that this was in the days before the use of mitomycin C. The results in the surgical arm were amazing—56 out of 57 surgeries were successful, for a success rate of 98%.

A successful trabeculectomy bleb. IMAGE COURTESY OF HENRY D. JAMPEL, MD, MHS

Cognizant of the results from England and aware that many of his own patients were much happier after surgical treatment of their glaucoma than they were when medically treated, Dr. Paul Lichter at the University of Michigan conceived of a large study in the United States to determine whether trabeculectomy or medical treatment was the preferable initial approach to newly diagnosed glaucoma.

At the time, around 1990, medical treatment was much more limited than it is today. There were no prostaglandins, no topical carbonic anhydrase inhibitors, and no alpha-adrenergic agonists. Pilocarpine, with its tendency to decrease vision through pupillary constriction, and oral carbonic anhydrase inhibitors, with their myriad systemic side effects, were in common use. Thus the “downside” of medical therapy was considerable. Some patients treated with pilocarpine, timolol and acetazolamide pills would recuperate from filtration surgery and suddenly feel better, see better, have more energy and be free of the need to take eye drops.

In this environment, the Collaborative Initial Glaucoma Treatment Study (CIGTS) was launched. A groundbreaking feature of the study was the incorporation of quality-of-life assessment, not as an afterthought, but as an integral part of the study. In addition to the traditional methods of evaluating the success of glaucoma intervention—visual acuity, visual field, IOP—subjects in the CIGTS underwent a 45-minute quality-of-life telephone interview at the beginning of the study and then every six months. This interview explored the ability of patients to carry out the activities of daily living, assessed their mood, and elicited ocular and systemic side effects attributable to medications or surgery.

The CIGTS enrolled and followed patients over the course of a decade and was successful in answering the questions of whether medications or surgery performed initially provided better glaucoma control and better quality of life over a five-year period. The bottom line: initial eye drops and initial trabeculectomy were roughly equivalent in preserving vision at five years,⁷ and at the five-year time point there were no major differences in quality of life assessment.⁸ However, during the first two years after surgery there was greater reporting of local symptoms in the surgery group than the medication group.

CIGTS Conclusions

Based on the aggregate results, what does the CIGTS teach us when we are discussing therapeutic options with a newly diagnosed glaucoma patient? Well, it has taught us that trabeculectomy is a reasonable first option—it need not be a last resort. On the other hand, although marginal improvements in trabeculectomy have been made in the last 15 years, as we get cleverer at avoiding surgical complications, significant improvements have been made on the medical side; a host of new, potent, well-tolerated topical agents for lowering the intraocular pressure are now available. It is quite possible that were the CIGTS repeated today, given the better medical options available, that medication would, in general, trump trabeculectomy in either effectiveness, safety or both. For this reason, on the whole, the role for initial trabeculectomy in the initial management is limited.

Although trabeculectomy as initial management cannot be recommended in general, there are specific instances in which it may be entertained. The CIGTS investigators reported on outcomes after stratifying their subjects by amount of glaucoma damage.⁹ In individuals with a worse mean deviation in the visual field at baseline, initial surgery appeared to be more effective than initial medical therapy.

Although one must be cautious in drawing too strong a conclusion from such post-hoc analyses, it is clear that what is best for glaucoma patients in general may not be best for any one glaucoma patient in particular. The argument that one should move more quickly to incisional surgery in a patient presenting with severe damage, as opposed to taking an extended period of time to assess the effectiveness of a medical regimen and a patient's adherence, is compelling.

Other Surgical Alternatives?

What about surgery other than trabeculectomy? The Primary Tube vs. Trabeculectomy study is comparing trabeculectomy to aqueous drainage device surgery as the initial surgical intervention, but not as the initial intervention before medications. Other procedures are now available, such as Trabectome, canaloplasty and endolaser cyclophoto-coagulation, and others may soon become available, such as the iStent.

However, none of these has been shown to be superior to trabeculectomy. Therefore, the use of these procedures as the first approach to lowering intraocular pressure in glaucoma patients is not warranted. Should further research demonstrate that any of these procedures have a safety profile superior to a trabeculectomy, they could assume a role in the initial treatment of glaucoma.

Putting the Options on the Table

When I first determine that a patient needs intraocular pressure lowering, I tell the patient that there are three ways to lower the intraocular pressure: eye drops, in-office laser treatment or intraocular surgery. I explain that glaucoma is a chronic, slowly progressive disease, and that rigorous studies and clinical guidelines suggest that both eye drops and in-office laser treatment are good initial approaches.

For patients who present with either advanced damage or very high IOPs unlikely to be lowered enough by either eye drops or laser, I may recommend a brief trial of medical therapy, because it sometimes will have a dramatic effect. But I also prepare the patient for the likelihood of early surgery. I look forward to the day when I can offer my patients an invariably successful operation without side effects, but we are not there yet. OM

References

1. Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK 2nd, Wilson MR, Gordon MO. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:701-713.
2. Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M; Early Manifest Glaucoma Trial Group Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120:1268-1279.
3. Nordstrom BL, Friedman DS, Mozaffari E, Quigley HA, Walker AM. Persistence and adherence with topical glaucoma therapy. Am J Ophthalmol. 2005;140:598-606.
4. Hennessy AL, Katz J, Covert D, Protzko C, Robin AL Videotaped evaluation of eyedrop instillation in glaucoma patients with visual impairment or moderate to severe visual field loss. Ophthalmology. 2010;117:2345-2352.
5. Jay JL, Murray SB. Early trabeculectomy versus conventional management in primary open-angle glaucoma. Br J Ophthalmol. 1988;72:881-889.
6. Migdal C, Gregory W, Hitchings R. Long-term functional outcome after early surgery compared with laser and medicine in open-angle glaucoma. Ophthalmology. 1994;101:1651-1656.
7. Lichter PR, Musch DC, Gillespie BW, Guire KE, Janz NK, Wren PA, Mills RP; CIGTS Study Group. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001 Nov;108(11):1943-1953.
8. Janz NK, Wren PA, Lichter PR, Musch DC, Gillespie BW, Guire KE, Mills RP; CIGTS Study Group The Collaborative Initial Glaucoma Treatment Study: interim quality of life findings after initial medical or surgical treatment of glaucoma. Ophthalmology. 2001 Nov;108(11):1954-1965.
9. Musch DC, Gillespie BW, Lichter PR, Niziol LM, Janz NK; CIGTS Study Investigators. Visual field progression in the Collaborative Initial Glaucoma Treatment Study the impact of treatment and other baseline factors. Ophthalmology. 2009;116:200-207.

Dr. Jampel is a Professor of Ophthalmology at Wilmer Eye Institute of Johns Hopkins University School of Medicine in Baltimore.