Exfoliative glaucoma can prove to be a particularly difficult disease for opthalmologists to manage. In this article, aspects of IOP-lowering therapy specific to this type of glaucoma are considered, as well as the range of treatments available and the potential advantages and challenges associated with each therapy.
Take-home message: Exfoliative glaucoma can prove to be a particularly difficult disease for opthalmologists to manage. In this article, aspects of IOP-lowering therapy specific to this type of glaucoma are considered, as well as the range of treatments available and the potential advantages and challenges associated with each therapy.
By Faye Emery, Reviewed by Dr Gábor Holló, MD, PhD, DSc
Exfoliative glaucoma (XFG) typically presents in patients older than 60 years with glaucomatous optic nerve head damage and elevated IOP. In the majority of these patients significant optic nerve head and visual field damage is already present at diagnosis. Conversion from exfoliative syndrome (XFS) to XFG is considered to happen as a result of environmental factors increasing oxidative stress in the anterior chamber.
To provide long-term disease stability in XFG patients, a low mean IOP (<17 mmHg) and a narrow 24-hour IOP fluctuation should be acheived. Careful follow-up of XFS patients is essential to assess IOP levels and monitor for early glaucomatous structural and functional changes; this will help detect transition to XFG.
The following aspects need to be considered for successful long-term XFG management:
Medical management of XFG
Achieving a sufficiently low 24-hour target IOP with medical therapy is more difficult in XFG than in primary open-angle glaucoma (POAG).
Treatment: Prostaglandin analog topical therapy (e.g. latanoprost, travoprost and bimatoprost)
Advantages: Once-daily dosing is convenient and can be easily performed by another person (e.g. a family member) in elderly patients who are unable to administer therapy themselves. This topical therapy is also free of the systemic side effects associated with topical beta blockers. In a 3-month, prospective, multicentre study in XFG patients, evening-dosed latanoprost 0.005% provided somewhat greater IOP reduction and smaller diurnal IOP fluctuation than twice-daily timolol 0.5% monotherapy.
Challenges: Although prostaglandin monotherapies provide greater 24-hour IOP reduction from an untreated baseline in XFG compared with POAG, a particularly low target IOP is needed to prevent progression in XFG. As a result, combined therapy is often needed in XFG. More evidence is needed to determine an optimal stepwise approach to therapy for XFG.
Treatment: Fixed combination therapy
Advantages: Fixed combination therapies generally provide greater IOP reduction and lower mean IOP than monotherapies; an IOP reduction of 31%–36% from untreated baseline is achieved with various once-daily prostaglandin/timolol fixed combinations.
Challenges: Currently, no controlled data on combinations of three or more IOP-lowering products (for example, a prostaglandin/timolol fixed combination and a topical carbonic anhydrase inhibitor) are available specifically in XFG.
Argon laser trabeculoplasty (ALT) has been used to treat OAG since 1979; ALT lowers IOP by enhancing aqueous humor outflow through the trabecular meshwork. Other photocoagulative lasers have also been widely used for trabeculoplasty, with similar effectiveness.
Selective laser trabeculoplasty (SLT) was introduced in 1998 and selectively targets pigmented trabecular meshwork cells without photocoagulation. The procedure utilises a frequency-doubled Q-switched Nd-YAG laser to deliver relatively low energy in a large spot diameter (400 μm) to the trabecular meshwork surface.
Treatment: Argon laser trabeculoplasty
Advantages: As eyes with XFG typically exhibit moderate to dense pigmentation in at least part of the trabecular meshwork, ALT can be considered in most cases. In high-pressure XFG eyes, ALT frequently provides a large IOP reduction in the early post-laser period for months or even years. According to a retrospective study in 28 POAG patients and 26 XFG patients who were on maximal tolerated medical treatment prior to ALT, the cumulative probability of success with ALT after approximately 8 months was 77% and 59% for POAG and XFG patients, respectively (failure was defined as IOP >22 mmHg, 4–6 months after ALT, or the need for filtering surgery).
Challenges: Efficacy of ALT gradually diminishes over time (possibly due to continuous deposition of exfoliation material and pigment granules within the trabecular meshwork) and can only be assessed 4–6 weeks after treatment. In addition, care must be taken to prevent or adequately treat the IOP spikes that frequently occur within hours following treatment.
Treatment: Selective laser trabeculoplasty in exfoliative glaucoma
Advantages: As SLT does not cause a thermal effect (unlike ALT), it does not result in coagulative or disruptive changes in the trabecular meshwork and so can be successfully repeated in eyes that have previously undergone ALT or SLT. One 6-month randomised trial in 76 eyes (60 patients with XFG or XFS and elevated IOP, all poorly controlled with topical medication) found that IOP reduction with SLT and ALT was similar (6.8 mmHg and 7.7 mmHg, respectively, P = 0.56), and that a similar proportion of exfoliation patients (73%) showed an IOP reduction of at least 20% with both treatments at the 6-month post-laser visit.
Both ALT and SLT can be considered in: elderly patients with suboptimal compliance; patients with a poor tolerance or contraindication to IOP lowering medication; and poor candidates for filtration surgery. Laser trabeculoplasty does not decrease quality of life and thus can be used as primary therapy in early-to-moderate XFG.
Challenges: Despite efficacy of SLT being comparable with that of ALT in eyes with POAG, published data on the comparative efficacy in XFG is limited. The procedure is also associated with limited long-term efficacy.
Treatment: Laser iridotomy
Advantages: Can be used in XFG cases in which lens dislocation due to zonular damage has caused secondary angle closure. The iridotomy technique and subsequent management do not differ from those used in primary angle closure.
Surgery is typically considered when medical or laser therapy has failed to achieve the target IOP; when disease progression occurs or is anticipated despite medical and laser therapy; and in cases of intolerance or inadequate adherence to medical therapy.
Trabeculectomy (typically combined with 5-fluorouracil mitomycin C) is widely considered as the gold standard surgery in advanced or progressing XFG. In deep sclerectomy (DS), aqueous humor percolates through the thin tissue of the trabeculodescemetic membrane that separates the anterior chamber from a surgically created “scleral lake”, and is absorbed intrasclerally and by the subconjunctival space. Viscocanalostomy is similar to DS, but involves injection of a high molecular weight viscoelastic material into Schlemm’s canal to dilate the lumen.
The ab interno trabeculotomy is a recently developed technique approved for treatment of open-angle glaucoma. This technique utilises the Trabectome™(Neomedix Inc, Tustin, CA, USA) instrument which contains a microelectrode handpiece with irrigation and aspiration pieces and is designed to ablate the trabecular meshwork and the inner wall of Schlemm’s canal. Trabecular aspiration (TA) is also a relatively new technique specifically designed for the treatment of XFG.60 In TA, aqueous humor outflow is increased via aspiration of exfoliation material and pigment. By exerting a 100–200 mmHg suction force for a few minutes using the aspiration port positioned on the trabecular meshwork, the extracellular debris is removed.
Advantages: Trabeculectomy may provide the low IOP level often necessary in XFG. Studies have shown that the long-term success of trabeculectomy in XFG may be better than that documented with POAG, and exfoliation patients may even progress at a lower rate than POAG patients after filtering surgery.
Challenges: Vitreous loss may occur due to zonular damage. In XFG patients, there is also a tendency for a more pronounced inflammatory reaction, hyphema from microneovascularisation of the iris, synechiae formation, clinically significant choroidal detachment and choroidal hemorrhage, and cataract formation – all of which can complicate the surgery.
Treatment: Deep sclerectomy
Advantages: If aqueous humor percolation is insufficient, Nd-YAG laser goniopuncture can be performed to increase aqueous egress. As limited outflow is achieved with DS, hyperfiltration, hypotony, anterior chamber shallowing, cataract formation, and endophthalmitis are all exceedingly rare complications. In a randomised study, the effectiveness of DS was increased by intraoperative application of mitomycin C. The recently developed technique of CO2 laser-assisted DS is reported to be at least as effective as conventional DS in XFG eyes. In a prospective study of 24 XFG patients and 25 POAG patients found DS to be more effective in the XFG patients. The proportion of eyes with complete success (IOP <19 mmHg without medication) was 60.7% versus 37.9% for XFG and POAG, respectively.
Challenges: No direct comparison of efficacy between trabeculectomy and DS in XFG eyes is currently available.
Advantages: In a prospective case series, 60% of 57 glaucomatous eyes (14 of which had XFG) had IOP <21 mmHg without medication after 60 months following viscocanalostomy.56 The efficacy of combined phacoemulsification and viscocanaloplasty in 30 medically uncontrolled XFG eyes with cataract has also been investigated.57 Investigators found that all eyes achieved success (defined as an IOP <21 mmHg with or without medication) and 90% of the eyes achieved complete success (defined as an IOP <21 mmHg without medication).
Challenges: To date, there is limited information on the efficacy of viscocanalostomy specifically in XFG.
Treatment: Ab interno trabeculotomy
Advantages: The procedure is performed under gonioscopic view through a 1.6–1.8 mm size limbal side-port after the anterior chamber is filled with viscoelastic material. A 12-month non-randomised trial compared ab interno trabeculotomy alone and in combination with cataract extraction and intraocular lens implantation, respectively, between XFG and POAG patients.59 In the ab interno trabeculotomy only analysis (67 cases with XFG, 450 cases with POAG) the IOP reduction was greater in XFG (12.3 ± 8.0 mmHg) than in POAG (7.5 ± 7.4 mmHg, P<0.01) and the cumulative probability of success was 79.1% in XFG patients and 62.9% in POAG patients (P = 0.004). In the combined ab interno trabeculotomy plus cataract surgery analysis (45 cases with XFG, 263 cases with POAG) the cumulative probability of success was similar between the two types of glaucoma (86.7% in XFG and 91.0% in POAG; P = 0.73). The authors concluded that overall, ab interno trabeculotomy with the Trabectome offers greater IOP reduction in XFG eyes.
Challenges: Ab interno trabeculotomy is a relatively new procedure so published evidence regarding efficacy is limited.
Treatment: Trabecular aspiration
Advantages: Several clock hours of the trabecular meshwork can be treated by using a sweeping motion. In a prospective TA study conducted in 22 eyes of 19 patients with uncontrolled XFG, the mean preoperative IOP on medication was 31.3 mmHg, which decreased significantly to 16.8 mmHg by 18 months after TA. After surgery, 45% of the patients required no IOP-lowering medication. The procedure resulted in few complications (such as blood reflux from Schlemm’s canal and minor descemetolysis) and were not serious.60
Challenges: The procedure is best combined with cataract surgery. Trabecular aspiration is a relatively new procedure so published evidence regarding efficacy is limited.
The unique clinical attributes of this challenging glaucoma, i.e., rapid rate of progression and worse prognosis compared with POAG, mean that a tailored and more proactive management strategy is needed to prevent visual loss. The continuous synthesis of exfoliative material, along with a gradual buildup of pigment within the outflow system, and an extensive spectrum of pathophysiological alterations in the anterior segment of the eye (e.g., increased oxidative stress, higher aqueous levels of endothelin 1), necessitates closer monitoring to ensure therapy is successful and remains appropriate.
In XFG, combined therapy is needed earlier and more often and in certain at-risk cases, a fixed combination may be indicated as first-choice therapy. Argon and selective laser trabeculoplasty are effective and may be selected earlier in the treatment regimen, as either primary or adjunctive therapy options. It is important to note however, that many XFG cases will require timely surgery to obtain a low target 24-hour IOP of below 18 mmHg. In addition, laser trabeculoplasty may be insufficient in high-risk XFG patients with advanced visual field and disc damage, who often require a target IOP of <17 mmHg.
Trabeculectomy with an adjunctive antimetabolite remains the gold standard surgical option in XFG, however last decade has seen the introduction of other potentially safer surgical modalities for consideration in the management of XFG. Ophthalmologists considering such options should be aware that there is currently limited controlled evidence on the long-term efficacy, safety benefits, and cost. Finally, ophthalmologists need to keep in mind that XFG is also a systemic disease and due to its spectrum of systemic vascular sequelae, consultation with the cardiologist or general practitioner may be necessary.
The content of this article is based on the following recently published open-access review:
All original references can be found within this review.
Dr Gábor Holló, MD, PhD, DSc
Dr Holló is a Professor of Ophthalmology and the Head of the Glaucoma and Perimetry Unit for the Department of Ophthalmology, Semmelweis University, Budapest. The content of this article is based on the original published review [review details]
Dr Holló declares no conflicts of interest relating to the content of this article.