m
Recent Posts
Connect with:
Sunday / July 12.
HomemieyecareThe Ocular Surface: Cataract Surgery and Glaucoma

The Ocular Surface: Cataract Surgery and Glaucoma

Ocular Surface Disease (OSD) is very common in the age group of patients that present for cataract surgery and, in many cases, the two conditions co-exist. It is also the case that many of these patients will be on glaucoma medications, often for many years.

The main risk factors for OSD are age, being female, and postmenopausal oestrogen therapy. This cohort of patients can prove to be a particular challenge to the cataract surgeon, requiring careful pre-operative management before cataract surgery is contemplated.1

Figure 1. Anterior segment angiography highlighting drainage of aqueous after iStent inject implantation (image supplied by Dr Alex Huang).

There is robust evidence in the literature that glaucoma medications result in significant associated ocular and systemic morbidity and that this effect becomes more pronounced the longer patients are on treatment.2,3

A number of studies have shown significant levels of ocular toxicity with changes in the corneal epithelium, corneal sensitivity, meibomian gland function, and secondary changes on the conjunctival epithelium. In some cases, significant levels of conjunctival scarring can result in abnormal forniceal anatomy and even symblepharon formation in some advanced cases due to surface toxicity.

The main culprit is the preservative found in most formulations known as Benzalkonium Chloride (BAK). This cationic surfactant has the capacity to dissolve the lipid phase of the tear film, thus aiding drug penetration through the cornea and the conjunctiva. Its main biocidal effect is against bacteria and some viruses, fungi and protozoa.4

In general, the antimicrobial activity of all preservatives is inversely proportional to the compatibility with the ocular surface.5 Excipients (pharmacologically inactive substances acting as carriers for the active components), free radicals and pH may also have an impact on the ocular surface in patients on glaucoma medications. These parameter levels were found to be considerably variable between different glaucoma medications.

Figure 2a. Design and dimensions of the iStent inject.

BAK has also been found to be toxic to trabecular meshwork cells. Laboratory studies have shown reduced cell numbers, growth and altered morphology and increased proapoptotic activity in the trabecular meshwork.6,7

Furthermore, an accumulation of BAK has been found in the trabecular meshwork of patients treated chronically (five to 10 years) with BAK preserved medications.8 This has led to the hypothesis that chronic BAK exposure might actually worsen glaucoma.

Another consequence of chronic medication use is fibroblast activation in the conjunctival space and over-expression of inflammatory markers in the conjunctiva. As a consequence of these effects, patients have higher rates of surgical failure when they undergo filtration or shunt surgery, resulting in a downward spiral of treatment failures – ultimately causing significant morbidity for these patients.

All of these effects can result in a significant reduction in the quality of life for patients and they often complain of chronic irritation, pain and grittiness. In severe cases, secondary epithelial changes can result in further visual loss due to an impaired refractive surface.

EFFECT OF BAK ON CRYSTALLINE LENS AND CATARACT SURGERY

BAK has been shown to strongly induce the expression of inflammatory mediators in lens epithelial cells compared with latanoprost or timolol.9 The Blue Mountains Eye Study and Ocular Hypertension Treatment Study both suggested higher rates of cataract formation in those on antiglaucoma therapy.10,11

Figure 2b The device in situ within the angle, two years post implantation.

Miyake et al conducted studies that suggested that BAK preserved drops prior to cataract surgery increased the risk of cystoid macular oedema.12 This may be true in some patients, although some authors have suggested that this effect is more likely in patients that had complicated cataract surgery with a breach in the posterior capsule at the time of surgery.

GLAUCOMA MEDICATIONS, PRESERVATIVES AND GLAUCOMA SURGERY

A number of studies have shown the detrimental effect of medications and preservatives on the success of future glaucoma surgery and in particular filtration surgery. In one study of 124 trabeculectomies, they found that a higher rate of failure was associated with long-term usage of multiple medications (all preserved, including miotics and sympathomimetics) and corresponding subclinical inflammatory changes in the conjunctiva.13

In another retrospective study of 128 trabeculectomies, they compared BAK exposure using the number of BAK containing drops as a proxy and the dose corrected BAK exposure per day (adjusting for varying concentrations of BAK in different drops). Those with a higher number of preoperative drops and a higher dose corrected exposure had a higher risk of early trabeculectomy failure.14

Another study explored tear cytokines that demonstrated elevated levels of an inflammatory mediator (monocyte chemoattractant protein-1 (MCP-1)) in patients taking glaucoma medications. Higher levels of MCP-1 were found with longer duration of medication use (mostly BAK preserved).15

Figure 4a. Toxic epitheliopathy in a patient prior to iStent inject surgery. The patient was on a preserved prostaglandin analogue (PGA). Fine punctate erosions of the cornea are evident centrally.

THE ADVENT OF MIGS

The arrival of Minimally Invasive Glaucoma Surgery (MIGS) has transformed the way we manage cataract patients with co-existing glaucoma. We now have the capacity to reduce or eliminate potentially toxic agents from the ocular surface and significantly improve the quality of life of patients who have been on drops for many years. Currently, there are a number of devices in the market but the main two categories are devices that are implanted in the subconjunctival space and those that are implanted in the vicinity of the trabecular meshwork. The latter pathway has the advantage of restoring physiological drainage through the trabecular meshwork (trans-trabecular pathway), sparing the conjunctiva for future surgery if required.

ADVANTAGES OF THE TRANS-TRABECULAR DRAINAGE PATHWAY

There are a number of inherent advantages in restoring trans-trabecular drainage in glaucoma patients. Trans-trabecular drainage is the natural pathway that normally drains aqueous humour under physiological conditions. Studies have shown the presence of an extensive network of aqueous channels that connect Schlemms Canal to the episcleral drainage plexus.

Figure 4b. Two months after surgery there is a marked improvement in the appearance of the epithelium as the PGA has been ceased. The patient was much happier as her eyes were more comfortable.

This pathway becomes impaired in open angle glaucoma patients at the level of the juxta-canalicular trabecular meshwork, resulting in a secondary IOP rise. Trans-trabecular drainage bypass devices are able to restore a normal pathway and reduce IOP (Figure 1).

Other advantages include sparing the conjunctiva for future surgery if this is deemed necessary and also not creating an aqueous reservoir (bleb), which is associated with other risks such as infection, dysaesthesia and failures requiring multiple interventions (needlings, revisions etc).

One other important parameter to consider is that devices like the iStent inject are so small that they do not create anatomical changes on the limbus or cornea. Hence the final predicted refractive outcomes from cataract surgery are not altered in any way.

This is important as other larger devices have been associated with bleb formation that can alter refractive outcomes and cause myopic shifts.

THE ISTENT INJECT

Figure 5a. This patient had combined Cataract and iStent inject procedure. Two glaucoma medications were ceased postop and the eye was more comfortable.

The iStent inject is a heparin-coated non-ferromagnetic titanium implant measuring 360 microns by 230 microns. It is designed to create a pathway through the trabecular meshwork into Schlemm’s canal to facilitate aqueous outflow, thereby decreasing IOP (Figure 2a&b).

Each injector is preloaded with two titanium stents, each having an 80 micron central lumen diameter, and four 50 micron side outlets to allow for multidirectional outflow.

Each stent is designed to carry the total amount of aqueous humour produced (average 2.5 ml/min) by the human body. The ab interno multiple stent placement is designed to increase access to more collector channels.

TECHNIQUE AND PLACEMENT OF THE ISTENT INJECT

In most cases, iStent inject implantation follows the completion of cataract surgery. Intracameral viscoelastic is used to deepen the angle and maintain the anterior chamber. The injector is advanced under direct gonioscopic view through the existing corneal incision to the nasal trabecular meshwork, where the first stent is implanted into Schlemm’s canal (Figure 3). Without withdrawing from the eye, the injector tip is repositioned laterally to implant the second stent approximately two to three clock hours away from the first stent. At completion of the procedure, viscoelastic is removed and proper sealing of the corneal incision is performed. The whole procedure takes a few minutes at most, in experienced hands. The post-operative care is the same as in standard cataract surgery.

RESULTS AND EFFICACY

Figure 5b. The right eye (unoperated) eye remains on two ongoing glaucoma medications. There is irritation and discomfort from ongoing eyedrop use.

iStent inject surgery has been shown to be effective in reducing IOP and drop use in patients with mild to moderate glaucoma. A number of studies over the past four years have highlighted these effects.

In a recent study published by Manning, 0% of iStent inject eyes were on multiple medications at 12 months, and 92.9% were medication-free at 12 months. Furthermore, this significant medication reduction was accompanied by an IOP reduction of almost 6mmHg versus baseline.16 Other studies have shown similar results. Clement et al has shown a reduction in IOP in 165 eyes. In this series, mean month 12 IOP reduced by 23.2% from 18.27±5.41mmHg preoperatively to 14.04±2.98mmHg (P,0.001), with 95.8% of eyes achieving month 12 IOP of 18mmHg or less vs 60.6% preoperatively. Mean number of medications at 12 months decreased by 71.5%, 0.47±0.95 vs 1.65±1.28 preoperatively; 76.4% of eyes were on zero medications vs 17.6% preoperatively (P<0.001); 14.5% of eyes were on two or more medications vs 46.7% preoperatively (P<0.001), and 98.2% of eyes maintained or reduced medications vs their preoperative regimen.17

There were no stent-related intraoperative complications, and cup to disc ratio, visual field, and visual acuity were all stable. Only three eyes with more advanced disease underwent additional glaucoma surgeries. In a recent editorial, Chan concludes that there is evidence in the literature to support the use of the iStent inject in patients with mild to moderate glaucoma on one to two medications without significant additional surgical risk to cataract surgery alone.18

Besides its pressure lowering effect, the use of the iStent inject can result in significant improvements in patients’ ocular surface, with reduction in corneal erosions in some patients but also chronic erythema of the conjunctiva (Figures 4 & 5).

As with any new device, there are concerns about safety of implantation apart from efficacy. The iStent inject appears to be inert as it is made from surgical grade titanium, which is very biocompatible. The implant is coated with heparin to prevent tissue overgrowth on the surgical site. Unlike other devices, it has no porcine or other animal derivatives which may be an issue for some patients with specific cultural practices.

The inert nature of titanium also renders the device hypoallergenic – this has been an issue with implantable devices containing other metals such as nickel for instance in orthopaedic and neurosurgical procedures.19,20,21,22

CONCLUSION

The iStent inject, as a trans-trabecular bypass shunt, exhibits effectiveness in combination with a high safety profile. In patients with combined cataracts and glaucoma, where drug intolerance is an issue, or there are issues with compliance and adherence to therapy, this combined procedure is a good alternative to improve pressure control. Additionally, it can improve quality of life for patients with this chronic and debilitating disease.

Dr Alex Ioannidis is a cataract and anterior segment specialist. He performs refractive cataract surgery offering premium intraocular lens technology and has a particular interest in managing patients with complex anterior segment diseases.

Dr Ioannidis has been performing iStent and iStent inject surgery over the past five years in a cohort of his glaucoma patients.

References

1. Cho YK, Kim MS. Dry eye after cataract surgery and associated intraoperative risk factors. Korean J Ophthalmol 2009;23:65-73

2. Asiedu K, Abu SL .The impact of topical intraocular pressure lowering medications on the ocular surface of glaucoma patients: A review. J Curr Ophthalmol. 2018 Sep 1;31(1):8-15

3. Fogagnolo P, Torregrossa G, Tranchina L, et al. Tear Film Osmolarity, Ocular Surface Disease and Glaucoma: A review. Curr Med Chem. 2019 Jul 25.

4. Pellinen P, Huhtala A, Tolonen A, et al. The cytotoxic effects of preserved and preservative-free prostaglandin analogs on human corneal and conjunctival epithelium in vitro and the distribution of benzalkonium chloride homologs in ocular surface tissues in vivo. Curr Eye Res.2012;37:145–54.

5. Tu EY. Balancing antimicrobial efficacy and toxicity of currently available topical ophthalmic preservatives. Saudi J Ophthalmol. 2014;28:182–7.

6. Kawa JE, Higginbotham EJ, Chang IL, et al. Effects of antiglaucoma medications on bovine trabecular meshwork cells in vitro. Exp Eye Res 1993;57:557–65.

7. Tripathi BJ, Tripathi RC, Millard CB. Epinephrine-induced toxicity of human trabecular cells in vitro. Lens Eye Toxic Res 1989;6:141–56.

8. Hamard P, Blondin C, Debbasch C, et al. In vitro effects of preserved and unpreserved antiglaucoma drugs on apoptotic marker expression by human trabecular cells. Graefes Arch Clin Exp Ophthalmol 2003;241:1037–43.

9. Goto Y, Ibaraki N, Miyake K. Human lens epithelial cell damage and stimulation of their secretion of chemical mediators by benzalkonium chloride rather than latanoprost and timolol. Arch Ophthalmol 2003;121:835–9.

10. Herman DC, Gordon MO, Beiser JA, et al. Topical ocular hypotensive medication and lens opacification: evidence from the ocular hypertension treatment study. Am J Ophthalmol 2006; 142:800–10.

11. Chandrasekaran S, Cumming RG, Rochtchina E, et al. Associations between elevated intraocular pressure and glaucoma, use of glaucoma medications, and 5-year incident cataract: the Blue Mountains Eye Study. Ophthalmology 2006;113:417–24.

12. Miyake K, Ibaraki N, Goto Y, et al. ESCRS Binkhorst lecture 2002: Pseudophakic preservative maculopathy. J Cataract Refract Surg 2003;29:1800–10.

13. Broadway DC, Grierson I, Stürmer J, et al. Reversal of topical antiglaucoma medication effects on the conjunctiva. Ophthalmol1996;114:262–7.

14. Boimer C, Birt CM. Preservative exposure and surgical outcomes in glaucoma patients: The PESO study. J Glaucoma 2013;22:730–5.

15. Öztürker ZK, Öztürker C, Bayraktar S, et al. Does the use of preoperative antiglaucoma medications influence trabeculectomy success? J Ocul Pharmacol Ther 2014;30:554–8.

16. Manning D. Real-world Case Series of iStent or iStent inject Trabecular Micro-Bypass Stents Combined with Cataract Surgery. Ophthalmol Ther. 2019 Aug 17

17. Clement CI, Howes F, Ioannidis AS, Shiu M, Manning D. One-year outcomes following implantation of second-generation trabecular micro-bypass stents in conjunction with cataract surgery for various types of glaucoma or ocular hypertension: multicenter, multi-surgeon study. Clin Ophthalmol. 2019 Mar 13;13: 491-499.

18. Chan HHL, Brooks AVM. What is the role of iStent in glaucoma management in 2019? Clin Exp Ophthalmol. 2019 Sep;47(7):835-836.

19. Kre ̨ cisz B, Kiec ́ -Swierczynska M, Chomiczewska- Sko ́ra D. Allergy to orthopedic metal implants—a prospective study. Int J Occup Med Environ Health. 2012;25(4):463–9.

20. Ahlstrom MG, Thyssen JP, Menne ́ T, Johansen JD. Prevalence of nickel allergy in Europe following the EU Nickel Directive—a review. Contact Dermatitis. 2017;77(4):193–200.

21. Grande A, Grewal S, Tackla R, Ringer AJ. Life-threatening allergic vasculitis after clipping an unruptured aneurysm: case report, weighing the risk of nickel allergy. Surg Neurol Int. 2014;5(Suppl 4):S161–4.

22. Schmidlin K, Verzwyvelt J, Bernstein D, Kim H. Probable delayed-type hypersensitivity to nickel- containing cerebral aneurysm clip associated with neurologic deficits. J Allergy Clin Immunol Pract. 2015;3:609–11.