Primary Open Angle Glaucoma in Africa: Prospects and Application of Lasers in African Eyes

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Background

Glaucoma is the leading cause of irreversible blindness in the world. [1]The number of people living with glaucoma was estimated to be 64.3million in 2013 and projected that by 2020, the figure will increase to 76.0 million. [1] Glaucoma in Africans tend to be more aggressive and resistant to conventional treatments. Therefore, it was not unexpected when reported that most of glaucoma blindness occurs in Africa.[2]Glaucoma treatment algorithm traditionally entails initial medical therapy to be followed by laser if medications fail or are inadequate to lower intra-ocular pressure to desired level. When laser fails, surgery is then recommended. Although there are different types of lasers with proven efficacy against glaucoma, treatment of glaucoma in Africa especially the sub-Saharan Africa largely involves the duo of medication and surgery with little or no availability of the intermediate laser treatment. High cost of anti- glaucoma medication coupled with fear of glaucoma surgery are the bane of glaucoma management in most African countries.[3] [4]Therefore, lasers, being less invasive and portable, offer glimmer of hope for glaucoma care in Africa.

Patient Selection

Generally, any patient diagnosed with POAG could benefit from laser treatment especially where target intra-ocular pressure (IOP) could not be achieved with maximum medical therapy. Recently, it has been shown that Selective Laser Trabeculoplasty is effective as primary treatment as such it could be used as primary intervention. Others forms of secondary glaucomas such as pseudo exfoliation or pigmentary glaucoma could also benefit from laser trabeculoplasty. However, Laser Trabeculoplasty is contraindicated in synechial Angle closure glaucoma, NVG, patients with corneal opacity, ICE syndrome and congenital glaucoma.With improved safety profile of laser cyclophotocoagulation, micropulse trans-scleral laser therapy is now being used in treating eyes with good vision.

Dr A Sadiq performing MLT in Nigeria

Indications

1.Adjuvant treatment of POAG

2.Primary Treatment of POAG

3.Treatment of some secondary open angle glaucoma

4.Treatment of refractory glaucoma

5.Treatment of failed glaucoma surgery

6.Treatment of pediatric glaucoma

7.Suturelyis post-trabeculectomy

8.Poor compliance with eye drop regimens

9.Difficulty using eye drops due to intolerance== Contraindications ==

Surgical Technique

CHOICE OF LASERS

1.Laser trabeculoplasty defined as application of laser to trabecular meshwork in order to improve facility of aqueous outflow. Wiser and Witter in 1979 introduced Argon Laser Trabeculoplasty(ALT) while Latina and Park described selective laser trabeculoplasty (ALT) in 1995.[5] [6]Several studies have demonstrated the efficacy and safety of the two procedures. [7][8]Micropulse Laser Trabeculoplasty(MLT) is the newest addition into the armamentarium[9]

A. Argon Laser Trabeculoplasty (ALT): This was first introduced in 1979 and it involves application of CW 514nm argon green or blue-green laser at the junction between the pigmented and non-pigmented portion of the trabecular meshwork. ALT brings about IOP reduction via creating some mechanical changes in trabecular meshwork that subsequently open up the drainage pathway or by stimulating biological activity in trabecular cells that leads to IOP reduction. The safety and efficacy of the laser has been reported in several studies.[7],[10][11]

B. Selective Laser Trabeculoplasty introduced in 1995 uses Q-switched ND-YAG and frequency-doubled ND YAG laser at pulse duration of 10 nanosec to 1 microsec selectively targeting pigmented portion of trabecular meshwork without collateral damage to adjacent tissues. SLT is thought to reduce IOP by stimulating cascade of cellular activities in trabecular meshwork that ultimately leads to increase facility of aqueous outflow.[6][12]

C. Micropulse Laser Trabeculoplasty: This relatively new techniques, instead of delivering the laser energy in a continuous wave, the energy is subdivided into short pulses with specific “on” and “off” times thereby minimizing the heat buildup and hence thermal damage to adjacent tissues. The off interlude allows the temperature of the target tissue to cool down before the next shot .It also fend off spread of energy to adjacent tissue.[9]

2. Laser cyclophotocoagulation refers to the use of laser energy to destroy ciliary processes. The energy absorbed by pigmented epithelium of ciliary body leads to coagulative necrosis of the tissue and subsequent reduction in aqueous production. Cyclophotocoagulation can be achieved with Nd-YAG or Diode laser. Currently, Diode Laser Cyclophotocoagulation has supplanted Nd-YAG CPC and it can be either Trans-scleral Diode Laser Cyclophocoagulation (TSCPC) or Endoscopic Cyclophocoagulation (ECP).[13]

A. Trans-scleral CPC :Trans-scleral CPC employs specifically designed probe contact plate which when placed at appropriate distance from the limbus ensures delivery of energy into the ciliary processes. Laser CPC is a treatment of last resort reserved for glaucoma unresponsive to maximum medical treatment, eyes that have failed filtration surgery or likely to fail future filtration surgery such Aphakic glaucoma, Neovascular glaucoma etc. Trans-scleral CPC could be performed with either continuous wave or Micropulse diode laser.[14]

1.Continuous Wave Trans-scleral CPC (CW-TSCPC):The CW-TSCPC delivers continuously laser energy to the ciliary epithelium. Although it has been shown to be effective in treatment of refractory glaucoma, the reported deleterious side- effects such as hypotony and phthisis imputed to continuous laser delivery limited its utility in eyes with good vision.

2. Micropulse Trans-scleral Laser Therapy improves the safety profile of the procedure in that it releases energy in a form of repetitive pulses(on) interspersed with off cycle.[13] [15]The off interlude allows the target tissue to cool down and also prevent dissipation of energy to the adjacent tissue.

B. Endoscopic Cyclophotocoagulation involves direct application of laser to the targeted ciliary pigmented epithelium with little or no collateral damage to the adjacent ciliary muscle, ciliary body stroma or par plana and it can be combined with cataract surgery.

Laser Trabeculoplasty for Glaucoma: International Recommendations*
Treatment Parameters Argon Laser Trabeculoplasty Selective Laser Trabeculoplasty
Laser type Argon green or Blue green/Diode Laser Frequency doubled Q-Switched Nd:YaG Laser(532nm)
Spot size 50 microns (Argon) or 75 microns (Diode) 40 microns
Power 300 to 1000mW 0.5 to 2mJ
Application site TM junction non-pigmented/pigment Trabecular meshwork (TM)
Handheld Lens Goldmann gonioscopy lens or Ritch lens Goldman or SLT lens
Treated Circumferance 180-360 180-360
Number of Burns 50 per 180 degrees 50 per 180 degrees
Number of Settings 1 or 2
End points Blanching at junction of anterior non-pigmented and pigmented TM 

*copied from ICO guidelines for glaucoma care

Dr A Sadiq performing TSCPC in Nigeria

Cyclophotoocoagulation for Glaucoma: International Recommendations**

Treatment Parameters Transscleral Diode Laser 
Laser Type Diode Laser 
Power 1.0 to 2.5 W 
Exposure Time 0.5 to 4.0 seconds 
Application Site  1.0 to 2.0 mm from limbus 
Handheld Probe  Transscleral contact 
Treated Circumference  180 – 360 degrees 
Number of Burns  ~ 12 – 20 spots per 180 degrees 
Number of Sittings  1 or 2 

**copied from ICO guidelines for glaucoma care

Outcomes

1.IOP Reduction: Selective Laser trabeculoplasty has been shown to be effective in IOP reduction and the percentage IOP reduction as well as mean IOP decrease varies between studies.[6],[16][17][18] In South Africa, Goosen et al [19]reported 32.0% (20mmHg to 13.6mmHg) IOP reduction from baseline and observed no difference in response between males and females patients. Similarly, Seck et al[20] retrospectively reviewed 69 eyes of 40 black patients 12 months after treatment with SLT. The results showed that 90% of patients had mean IOP decrease of 2.3 ± 1 mmHg and SLT permitted discontinuation of a prostaglandin in 60% (42 cases). Similarly, Micropulse Laser Trabeculoplasty has also been shown to cause 17.2% reduction from baseline among Nigerian eyes.[18]

2.Impact on Anti-Glaucoma Medication: Glaucoma patients incur financial burden as well as side-effects as result of prolonged use of antiglaucoma medication. Ahmed et al [21] found significant reduction in anti-glaucoma medication from 2.25 ± 0.97 before SLT treatment to 1.0 (±1.3) at the end of 18 months follow-up (P= 0.004).

3.Laser as Primary Treatment: The seminal LiGHT trial[8], though not conducted on African eyes, described how target intraocular pressure was achieved without intraocular pressure medication in 419 (78·2%) of 536 eyes treated with selective laser trabeculoplasty as primary treatment. Additionally, in Nigeria, Abdul et al [22]demonstrated that 83% of POAG had a drop in IOP of >30% at 12 months after primary treatment with continuous trans-scleral cyclophotocoagulation and only 9% were on medication at the final follow up.

Complications

Complications associated with laser trabeculoplasty include acute IOP elevation, uveitis, peripheral anterior synechia, corneal burns and hyphema [12]while trans-scleral cyclophotocoagulation could be complicated by hyptony, drop in vision, phthisis and severe inflammation.[13]

Conclusion: With huge annual cost of glaucoma medication in sub-Saharan Africa[23] and proven efficacy of laser procedures in treatment of PAOG, laser treatments should be encouraged and be made more available and affordable to glaucoma care- givers in Africa.

References

  1. 1.0 1.1             Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis. Ophthalmology. 2014;121(11):2081-2090. doi:10.1016/j.ophtha.2014.05.013
  2. Kyari F, Abdull MM, Bastawrous A, Gilbert CE, Faal H. Epidemiology of glaucoma in sub-saharan Africa: prevalence, incidence and risk factors. Middle East Afr J Ophthalmol. 2013;20(2):111-125. doi:10.4103/0974-9233.110605
  3. Ad koya BJ, Akinsola FB, Balogun BG, Balogun MM, Ibidapo OO. Patient refusal of glaucoma surgery and associated factors in Lagos, Nigeria. Middle East Afr J Ophthalmol. 2013;20(2):168-173. doi:10.4103/0974-9233.110612e
  4. Adio AO, Onua AA. Economic burden of glaucoma in Rivers State, Nigeria. Clin Ophthalmol. 2012;6:2023-2031. doi:10.2147/OPTH.S37145
  5. James B, Witter SL. A Pilot Glaucoma. ArchOphthalmol. 1979;97:319-322.
  6. 6.0 6.1 6.2 Latina MA, Park C. Selective targeting of trabecular meshwork cells: In vitro studies of pulsed and CW laser interactions. Exp Eye Res. 1995;60(4):359-371. doi:10.1016/S0014-4835(05)80093-4
  7. 7.0 7.1 Investigators TA. The advanced glaucoma intervention study (AGIS): 1. Study design and methods and baseline characteristics of study patients. Control Clin Trials. 1994;15(4):299-325. doi:10.1016/0197-2456(94)90046-9
  8. 8.0 8.1 Gazzard G, Konstantakopoulou E, Garway-Heath D, et al. Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial. Lancet. 2019;393(10180):1505-1516. doi:10.1016/S0140-6736(18)32213-X
  9. 9.0 9.1 Ma A, Yu SWY, Wong JKW. Micropulse laser for the treatment of glaucoma: A literature review. Surv Ophthalmol. 2019;64(4):486-497. doi:10.1016/j.survophthal.2019.01.001
  10. Krug J, Chiavelli M, Borawski G, et al. The Glaucoma Laser Trial (GLT) and glaucoma laser trial follow-up study: 7. Results. Am J Ophthalmol. 1995;120(6):718-731. doi:10.1016/s0002-9394(14)72725-4
  11. Wilensky JT, Jampol LM. Laser Therapy for Open Angle Glaucoma. Ophthalmology. 1981;88(3):213-217. doi:10.1016/S0161-6420(81)35047-7
  12. 12.0 12.1 Garg A, Gazzard G. Selective laser trabeculoplasty: Past, present, and future review-article. Eye. 2018;32(5):863-876. doi:10.1038/eye.2017.273
  13. 13.0 13.1 13.2             Dastiridou AI, Katsanos A, Denis P, et al. Cyclodestructive Procedures in Glaucoma: A Review of Current and Emerging Options. Adv Ther. 2018;35(12):2103-2127. doi:10.1007/s12325-018-0837-3
  14. Abdelrahman AM, El Sayed YM. Micropulse Versus Continuous Wave Transscleral Cyclophotocoagulation in Refractory Pediatric Glaucoma. J Glaucoma. 2018;27(10):900-905. doi:10.1097/IJG.0000000000001053
  15. Hirabayashi MT, Rosenlof TL, An JA. Comparison of Successful outcome Predictors for MicroPulse® Laser Trabeculoplasty and Selective Laser Trabeculoplasty at 6 months. Clin Ophthalmol. 2019;13:1001-1009. doi:10.2147/OPTH.S205977
  16. Damji KF, Bovell AM, Hodge WG, et al. Selective laser trabeculoplasty versus argon laser trabeculoplasty: Results from a 1-year randomised clinical trial. Br J Ophthalmol. 2006;90(12):1490-1494. doi:10.1136/bjo.2006.098855
  17. Onakoya AO, Olowoyeye AO, Onyekwelu OMA, Abikoye TM. Intraocular Pressure Changes Post Selective Laser Trabeculoplasty in the Contralateral Untreated Eyes of Nigerian Patients With Primary Open Angle Glaucoma. Nig Q J Hosp Med. 2015;25(2):133-138.
  18. 18.0 18.1 Babalola OE. Micropulse diode laser trabeculoplasty in nigerian patients. Clin Ophthalmol. 2015;9:1347-1351. doi:10.2147/OPTH.S82678
  19. Goosen E, Coleman K, Visser L, Sponsel WE. Racial Differences in Selective Laser Trabeculo-plasty Efficacy. J Curr Glaucoma Pr. 2017;11(1):22-27. doi:10.5005/jp-journals-10008-1216
  20. Seck SM, Agboton G, Dieng M, et al. La trabéculoplastie au laser sélectif (TLS): notre expérience chez le noir africain. J Fr Ophtalmol. 2015;38(3):238-246. doi:10.1016/j.jfo.2014.11.002
  21. Abdelrahman A, Eltanamly R. Selective laser trabeculoplasty in Egyptian patients with primary open-angle glaucoma. Middle East Afr J Ophthalmol. 2012;19(3):299-303. doi:10.4103/0974-9233.97930
  22. Abdull MM, Broadway DC, Evans J, Kyari F, Muazu F, Gilbert C. Safety and effectiveness of primary transscleral diode laser cyclophotoablation for glaucoma in Nigeria. Clin Exp Ophthalmol. 2018;46(9):1041-1047. doi:10.1111/ceo.13328
  23. AF S, G N, A M, et al. Glaucoma Control Strategies in Sub-Saharan Africa: A Review of the Clinical and Health Economic Evidence. Ophthalmic Epidemiol. 2018;25(5-6). doi:10.1080/09286586.2018.1501499