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Clear Lens Extraction in Primary Angle-closure Disease—Pros and Cons

Cataract extraction for management of primary angle-closure disease has been successfully practiced for many years. However, the extraction of a clear lens for glaucoma management, when visual symptoms are minimal, is a controversial subject. A few studies have reported on the outcomes of clear lens extraction without resorting to conventional methods, such as drugs and lasers. Others have compared clear lens extraction with trabeculectomy or iridotomy. Most have reported successful outcomes with this surgical modality, in terms of intraocular pressure control, reduction in the number of glaucoma medications, opening of the anterior chamber angle, visual gain, and improvement in quality of life. Unfortunately, the studies on clear lens extraction are hampered by both positive and negative aspects in their execution. This review was undertaken to debate the points presented in the studies in order to have a better understanding of the advantages and disadvantages of clear lens extraction in primary angle-closure disease.

Wishart and Atkinson in chronic PACG patients. 19 Guning and Greve, in their study to compare extra-capsular cataract extraction with glaucoma filtering surgery in eyes with PACG, found better results with cataract extraction. 20 Hata et al., in their study of primary phacoemulsification in PACG, compared cataract extraction with peripheral iridotomy and found the former technique to be superior in terms of IOP control and reduction in glaucoma medications. 21  group, but noted that phacotrabeculectomy was associated with more surgical complications (26.2% versus 8.1% for phacotrabeculectomy and phacoemulsification, respectively). 23 In a review of phacoemulsification in patients with glaucoma, 12 studies on chronic PACG showed the procedure was successful in reducing IOP by 30% and glaucoma medications by 58%.
The review also reported four studies on acute PACG that showed an average 71% reduction from presenting IOP. 24 Cataract extraction for PACD has been practiced for many years with seemingly effective results. Such spectacular outcomes are also expected with CLE. However, due to the absence of visual symptoms in patients with clear lenses it becomes controversial whether to opt for CLE as a primary procedure and abandon the pharmacological and laser treatments used conventionally.

Studies on clear lens extraction
There are only a handful of reported studies regarding the effectiveness of CLE in clinical practice. However, Walland et al. have noted the appearance of such reports in non-peer-reviewed trade journals, indicating that it is being practiced on a wider scale than has been published. 25 The EAGLE study was probably one of the first to assess the role of CLE in PAC/PACG.  A summary of the outcomes in terms of IOP control, seen in the various studies mentioned above, is presented in Table 2. Based on the positive results seen in these studies, CLE is being advocated by its proponents as a first-line treatment option for PAC and PACG. 27

Cost-effectiveness and patient quality-adjusted life years
One of the co-primary endpoints of the EAGLE study was to assess the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained after 36 months of treatment. 1 The mean health service costs were higher in patients randomized to CLE, compared with standard care:

Intraoperative mechanisms
Several mechanisms have been proposed through which CLE reduces IOP.
Deepening of anterior chamber with viscoelastic and hydrostatic pressure

Negative aspects of studies on clear lens extraction
PACD is not a single disease entity; rather, it is a continuum of different stages. Thus, each individual can be unique in terms of disease stage, and the management profile has to be tailored based on that particular stage.
The International Society of Geographic and Epidemiologic Ophthalmology has classified PACD into primary angle-closure suspect (PACS), primary angle-closure (PAC), and PACG. 37 Thomas 36 Therefore, not performing a procedure that is safe, easy and effective, such as peripheral iridotomy or iridoplasty, and waiting 4-8 weeks to perform a CLE, appears to be improper.

Peripheral anterior synechiae
The presence of peripheral anterior synechiae is regarded as an indication for CLE, as peripheral iridotomy may not be effective. Nonetheless, in a study by Lai et al., some eyes with only 90 degrees of angle-closure following cataract extraction required glaucoma medications, while others with >270 degrees of angle-closure did not. 33 Chen et al. have also mentioned that IOP reduction following lens extraction does not seem to be related to the extent of peripheral anterior synechiae prior to surgery, but is more related to angle width. 24 Gonioscopy, conducted before lens extraction,

Refractive outcomes
Patients with glaucoma have an increased propensity to show postoperative refractive surprises compared with the healthy population. In a study conducted at the University of Colorado, USA, significantly higher frequency of both small and large magnitude of refractive surprises were found in patients with glaucoma, as compared with patients without glaucoma. 46 The postoperative prediction of the effective lens position significantly relies on anterior chamber depth estimates, and is considered a major limiting factor in modern IOL power calculations. 47 Other factors, such as corneal curvature, axial length and lens vault, are also variable in patients with PACD or not included in formulas to calculate IOL power. 30,48 US OPHTHALMIC REVIEW In the EAGLE study, visual acuity was better in the CLE group compared with the standard care group by just three ETDRS letters. The authors of the EAGLE study pointed out that "while this magnitude of change is unlikely to be clinically important, it points to the overall improvement in visual function associated with CLE." 1 It is possible that the so-called clear lenses in the EAGLE study had some degree of nuclear sclerosis and developed a "refractive surgery effect" following CLE. 49 Day et al., in their analysis of the EAGLE study, agreed that refractive predictability was sub-optimal. 50 In the study by Lam et al., postoperative visual gain was persistently better in the phacoemulsification group compared with the standard care group, but not statistically significant. 39 Loss of accommodation following CLE in a relatively young population should also be considered.

Perioperative complications
Laser peripheral iridotomy and iridoplasty are effective office procedures and can be performed immediately on assessing the need for intervention. 51,52 Conversely, lens extraction has to be planned and patients are often skeptical of surgical options. In developing countries, patients often need to discuss the situation with families, as well as arrange finances for surgery.
This requires an intervening period, which may last for months at times.
Patients occasionally travel long distances to reach centers equipped for laser/surgical procedures. To delay a simple office procedure such as peripheral iridotomy may prove disastrous, as the patient may develop an AAC attack during the waiting period.
Immediately prior to surgery, the pupil has to be dilated. The risk of developing an acute AAC attack due to pupillary dilatation has to be kept in mind. 53 PAC eyes have thick, large lenses with shallow anterior chambers. During surgery, there is less room for the surgeon to maneuver the bulky nucleus in the confined space. This may force the surgeon to apply phaco power near the corneal endothelium. 10 Studies on cataract extraction in PACD eyes have reported postoperative decreased corneal endothelial cell counts and corneal decompensation. 33,49,54 Individuals with a previous history of AAC may have decreased endothelial cell density by around 33% from baseline and are vulnerable for corneal decompensation. 22,33 Zonular instability may also be a factor in these patients. 5 Eyes with PACD may have atonic or atrophied irises, making pupillary dilatation difficult. This may also occur following long-term use of pilocarpine, or in the presence of significant posterior synechiae. In these situations, pupillary stretching by hooks, rings, or other maneuvers would be required. This increases the risk of iris trauma, hyphema, and chronic inflammation. The atonic iris may also cause intraoperative floppy iris syndrome and aggravate postoperative uveitis.
In the EAGLE study, complications encountered in the CLE group were as follows: intraoperative-posterior capsule tear (n=2; 1%), iris prolapse where none existed before CLE. These can cause psychological distress and financial burden on patients, as they have to travel frequently to the hospitals for follow-up. 56 Any surgical procedure also requires control of co-morbid conditions such as diabetes mellitus, systemic hypertension, infections, and inflammations. This is not a significant factor when performing peripheral iridotomy.

Regression to the mean
The significantly lowered IOP mentioned in many reports is often ascribed to the phenomenon of "regression to the mean". It implies that the statistically lowered postoperative IOP is an exaggerated effect on the relatively high preoperative IOP in the inclusion criteria. This makes the lowering of IOP from a very high level to lower levels statistically significant. 33 Chen et al.
have noted that "higher IOP is the single most significant factor associated with a greater IOP drop after phacoemulsification". 24 Similar results have also been reported by other authors. 11,49,[57][58][59] Baseline IOP in the EAGLE study was ≥30 mmHg and in Dada's study was ≥25 mmHg. 1,3 Therefore, the significant postoperative lowering in IOP seen in these studies could be attributed to regression to the mean.

Intraocular pressure
In the EAGLE study, preoperative IOP was ≥30 mmHg. Therefore, questions remain whether CLE would be useful if IOP is lower. 60 The mean postoperative IOP in the EAGLE study was 1 mmHg lower in the CLE group at 3-year follow-up. Clinically, this difference is small and statistically insignificant. 1 In Dada's study, good IOP control was noted for 12 months after CLE. 3 Whether this effect would be sustained beyond this period is not known. Vizzeri and Weinreb have opined that lens extraction alone may not be sufficient for long-term IOP control. 59 Studies show IOP reduction in eyes with PACG ranging from 2-12 mmHg. 28 However, the lowering of IOP is also dependent on trabecular and post-trabecular mechanisms. Dysfunction in these regions may not provide adequate lowering of IOP by CLE alone. 7,37 The effect of CLE on diurnal fluctuation of IOP is also questionable. 37  Secondly, in some countries, glaucoma medications are provided by government hospitals through a tax-paying or social-service mechanism.
However, most of these countries require the patient to pay for surgery, leading to the incremental cost of treatment.
Indices such as EQ-5D and Glaucoma Utility Index are largely dependent on visual status. Similarly, bilateral visual status forms the cornerstone of ICER.
The positive results in these parameters seen in the EAGLE study are likely due to improved contrast sensitivity and not angle-closure status. 42 The financial advantage mentioned in the EAGLE study is specific to the UK and may not be applicable in countries where insurance companies may refuse CLE due to a lack of visual complaints. In the EAGLE study, CLE would presumably be cost-effective only after 10 years of surgery. 28 The risks and benefits of surgery during such a period have to be taken into consideration.

Conclusion
CLE is being advocated as a method to primarily treat PACD without opting for other standard care modalities. The advocates for this procedure claim CLE has the advantage of treating the cause of PACD, i.e., the lens, thus the method is curative to some degree. However, like many surgical procedures, CLE is associated with increased risk of