LiGHT Trial: Selective Laser Trabeculoplasty vs. eyedrops

 

The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial is a multicenter randomized controlled trial comparing initial treatment using selective laser trabeculoplasty (SLT) with initial treatment with IOP-lowering eye drops.

The study was performed on treatment-naïve patients with open-angle glaucoma (OAG) or ocular hypertension (OHT), assessing health-related quality of life (HRQoL), cost-effectiveness, and clinical efficacy after 3 years.

The initial results of the LiGHT Trial were reported in 2019. The study found that initial treatment of OHT or OAG with SLT is more cost-effective than initial treatment with contemporary IOP-lowering eye drops after 3 years,

It also reported freedom from drops to 74.2% of patients, a reduced number of glaucoma surgeries, and very low rates of adverse events.

SLT was performed according to a predefined protocol at 360-degrees of the trabecular meshwork with 100 nonoverlapping shots (25 per quadrant; energy, 0.3-1.4 mJ).

For the first 36 months (3 years) of the trial, 1 additional SLT retreatment was allowed (total of 2 SLT treatments), and thereafter, the next escalation was medical treatment.

Single-drug eye drops were prescribed initially after randomization for patients in the drops arm and for patients whose IOP remained uncontrolled after SLT.

Different or additional eye drops were prescribed in the event of a treatment switch (e.g., adverse reaction) or treatment escalation (e.g., IOP above target).

Drug classes for first-line, second-line, or third-line treatment were defined according to NICE and the European Glaucoma Society guidance: first line, prostaglandin analogs; second line, bblockers; and third or fourth line, topical carbonic anhydrase inhibitors or a-agonists.

Fixed combination drops were allowed; systemic carbonic anhydrase inhibitors were permitted only as a temporary measure while awaiting surgery and were not considered a treatment escalation for the purposes of the analysis.

For the first 36 months (3 years) of the trial, patients initially randomized to receive IOP-lowering eye drops were not permitted SLT; failure to control IOP or OAG with eye drops resulted in surgical treatment (trabeculectomy).

After the first 3 years, patients were allowed a crossover, whereby they could opt to undergo SLT as a treatment switch, that is, to reduce medication load, or as a treatment escalation, that is, to avoid increasing medication load or to delay surgery.

Of the 692 patients who completed 3 years of the LiGHT Trial, 633 patients (91.5%) entered the 3-year extension (from 36 to 72 months); 313 patients (547 treated eyes) initially received SLT, and 320 patients (549 eyes) initially commenced treatment with IOP-lowering eye drops.

Of the 320 patients allocated to medication, 112 patients (176 eyes; 35% of patients) decided to undergo SLT immediately or shortly after the end of the 3-year monitoring period.

Drop-free IOP control at 72 months, was achieved in 69.8% of eyes initially treated with SLT compared with 18.0% of eyes initially treated with IOP-lowering eye drops.

At 72 months, 61.2% of eyes initially treated with eye drops were using 1 or 2 medications compared with 18.5% of eyes initially treated with SLT.

Data published previously have indicated that initial treatment with SLT may delay progression of OHT and OAG. VF analysis suggests more eyes initially treated with IOP-lowering eye drops undergo rapid VF progression compared with eyes first treated with SLT.

After 6 years of treatment, eyes initially treated with SLT demonstrated reduced objectively defined progression compared with IOP-lowering eye drops; this was achieved despite eyes initially treated with IOP-lowering eye drops achieving lower IOP at 6 years, possibly suggesting other protective roles of SLT.

Eyes initially treated with SLT needed fewer trabeculectomies. For the first 3 years after initial treatment, no trabeculectomies were needed in eyes receiving initial SLT. At 6 years, 3 times fewer eyes initially treated with SLT required a trabeculectomy, compared with eyes initially treated with eye drops.

Selective laser trabeculoplasty also leads to a reduced need for cataract surgery. 50% more eyes initially treated with eye drops needed cataract surgery during the 6- year course of the LiGHT Trial compared with eyes initially treated with SLT.

For the first 3 years of the LiGHT Trial, patients using drops experienced comparable HRQoL to those who received initial SLT, and these findings are supported further by the LiGHT Trial extension to 6 years.

The safety profile of SLT remains very good, with no sight-threatening complications. Intraocular pressure rose > 5 mmHg from IOP before treatment in only 1% of treated eyes, and of these, only 1 eye needed treatment.

FURTHER DETAILS ON SLT AVAILABLE HERE:

SELECTIVE LASER TRABECULOPLASTY

OMIDENEPAG: Omlonti, Eybelis

 

OMLONTI 0.002% (EYBELIS) eye drops is a new drug approved by FDA recently, for treatment of open angle glaucoma and ocular hypertension.

The drug has been developed jointly by Santen Pharmaceutical Co., Ltd. and UBE Corporation of Japan.

Omidenepag isopropyl, the active pharmaceutical ingredient in OMLONTI, is a relatively selective prostaglandin EP2 receptor agonist.

It increases aqueous humor drainage through the conventional (or trabecular) and uveoscleral outflow pathways, and the only product of this kind with this pharmacological action.

The FDA approval for OMLONTI was based on data from 12 clinical studies conducted in multiple global locations. Notably, a U.S. Phase 3 study confirmed OMLONTI to be non-inferior to timolol, the standard of care. Two different Phase 3 studies conducted in Japan and Asia showed OMLONTI to be non-inferior to latanoprost, another standard of care.

OMLONTI appears as a clear, colorless solution. It is supplied as a sterile, isotonic, buffered aqueous solution of omidenepag isopropyl with a target pH of 5.8 and an osmolality of approximately 285 mOsmol/kg.

Each mL of OMLONTI contains: 

Active: 0.02 mg of omidenepag isopropyl. Preservative: 0.005% benzalkonium chloride. Inactive ingredients: glycerin, polyoxyl 35 castor oil, sodium citrate, citric acid monohydrate, edetate disodium, sodium hydroxide and/or hydrochloric acid (to adjust pH), and water for injection.

Recommended Dosage:

The recommended dosage is one drop in the affected eye(s) once daily in the evening.

Side effects:

The most common adverse reactions seen with OMLONTI are conjunctival hyperemia (9%), photophobia (5%), vision blurred (4%), dry eye (3%), instillation site pain (3%), eye pain (2%), ocular hyperemia (2%), punctate keratitis (2%), headache (2%), eye irritation (1%), and visual impairment (1%).

The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of OMLONTI, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes are likely to be reversible.

Iris color change may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish.

OMLONTI may gradually change eyelashes and vellus hair in the treated eye. These changes include increased length, thickness, and the number of lashes or hairs. Eyelash changes are usually reversible upon discontinuation of treatment.

OMLONTI can induce ocular inflammation and should be used with caution in patients with active ocular inflammation, including iritis/uveitis.

OMLONTI can induce macular edema. It should be used with caution in aphakic patients, in pseudophakic patients, or in patients with known risk factors for macular edema.

Risk during pregnancy:

There are no available data on the use of OMLONTI in pregnant women. In animal reproduction studies, subcutaneous administration of omidenepag isopropyl to pregnant rabbits throughout the period of organogenesis produced fetal skeletal anomalies at a dose of 24 times the clinical dose, based on estimated plasma Cmax. Omidenepag isopropyl was not teratogenic in rats when administered subcutaneously at 1 mg/kg/day, 2,452 times the clinical dose, based on estimated plasma Cmax.

Risk during lactation:

Systemic exposure to omidenepag following topical ocular administration is low. it is not known whether measurable levels of omidenepag would be present in maternal milk following topical ocular administration. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for OMLONTI and any unknown potential adverse effects on the breast-fed child from OMLONTI.

Effect on male/female fertility:

There are no data on the effects of OMLONTI on human fertility. No impairment of fertility has been reported in animals receiving omidenepag isopropyl subcutaneously at doses up to 2,452 times the clinical dose based on estimated plasma Cmax.

Pediatric Use:

The safety and effectiveness of OMLONTI have not been established in pediatric patients.

ANECORTAVE ACETATE: A novel glaucoma treatment

 

Anecortave acetate (AL-3789) (Alcon Laboratories, Inc.) is a cortisene –a derivative of cortisol.

Anecortave is formulated by replacing the hydroxyl group at carbon 9 of the cortisol molecule with a double bond between carbons 9 and 11 and the addition of an acetate group at carbon 21.

This renders Anecortave devoid of glucocorticoid receptor agonist activity.

Anecortave acetate has two inherent pharmacological activities; it has antiangiogenic properties through inhibition of the angiogenic proteolytic cascade, and it has IOP-lowering activity.

It has been studied mostly in models of neovascular Age-related macular degeneration (AMD).

In these models it is given by posterior juxtascleral depot injection.

The agent has angiostatic activity by inhibition of proteases that degrade the extracellular matrix, thus blocking migration of vascular endothelial cells.

It has no glucocorticoid receptor-mediated biological activity.

Anecortave acetate does not reduce inflammation, elevate IOP, or cause cataracts.

In glaucoma it has been given by anterior juxtascleral depot (AJD). It exerts its effect locally, migrating through sclera over approximately 270°, and acting at the level of the trabecular meshwork (TM) and ciliary body, for a prolonged period.

Robin et al have described the delivery of this medication in the sub-Tenon’s space, creating a circumferential deposition surrounding the limbus. IOP was lowered by 40–50% at 4 weeks in eyes with baseline IOP ranging from 23 to 52 mmHg on a prostaglandin analogue. In six out of seven eyes, Anecortave acetate produced a rapid and substantial reduction in IOP, dropping by 9.5 mmHg after 1 week and by 12.7 mmHg at 4 weeks. This IOP lowering from a single injection lasted for at least 3 months and up to 19 months.

Prata demonstrated at least 30% IOP reduction lasting for at least 3 months after a single injection of Anecortave.

Callanan has also reported good IOP reduction following Anecortave injection. Doses of 12 mg, 24 mg, or 30 mg were given every 4 months.

Landry has also reported more than 30% IOP reduction with this injection.

In a series of steroid-induced glaucoma a rapid and sustained reduction in IOP was demonstrated by 1 week in all patients, and no adverse events were noted. By 1 month, seven of eight had IOP that remained reduced by over 30%.

The mechanism for Anecortave acetate’s IOP lowering is not fully understood at present.

Elevated plasminogen activator inhibitor-1 has been induced in cultured TM cells and found to be inhibited by simultaneous addition of Anecortave desacetate in the culture medium. This suggests the mechanism for this agent’s ability to lower IOP in patients with glaucoma and steroid-induced ocular hypertensive patients.

 

REFERENCES:

Robin AL, Suan EP, Sjaarda RN, Callanan DG, Defaller J; Alcon Anecortave Acetate for IOP Research Team. Reduction of intraocular pressure with anecortave acetate in eyes with ocular steroid injection-related glaucoma. Arch Ophthalmol. 2009 Feb;127(2):173-8. doi: 10.1001/archophthalmol.2008.595. PMID: 19204235.

Stalmans I, Callanan DG, Dirks MS, Moster MR, Robin AL, Van Calster J, Scheib SA, Dickerson JE Jr, Landry TA, Bergamini MV. Treatment of steroid-induced elevated intraocular pressure with anecortave acetate: a randomized clinical trial. J Ocul Pharmacol Ther. 2012 Dec;28(6):559-65. doi: 10.1089/jop.2012.0063. Epub 2012 Aug 3. PMID: 22860637; PMCID: PMC3505827.

T. A. Landry, J. Dickerson, J. C. Merriam; The Use of Anecortave Acetate for Refractory, Complex Glaucoma. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1206.

Prata TS, Tavares IM, Mello PAA, Tamura CY, Belfort R Jr. Anterior juxtascleral depot of anecortave acetate: intraocular pressure reduction in different types of glaucoma. Association for Research in Vision and Ophthalmology (ARVO); abstract 2008 E-1205, poster A47.

Callanan D, Fuller C, Landry TA, Dickerson JE, Bergamini MVW. Prophylactic anecortave acetate in patients with a retisert implant. Association for Research in Vision and Ophthalmology (ARVO) 2008; abstract 2008 E-5630

 

APHAKIC GLAUCOMA

 

Aphakic glaucoma was probably recognized for the first time by Bowman in 1865 (Bowman, W. 1865, Quoted by Duke Elder: System of Ophthalmology, 11, 722, Henry Kimpton, London, 1969).

Aphakic glaucoma is now quite rare in the adult population as most patients undergo cataract surgeries where the capsular bag and posterior capsule are left intact. In such cases intraocular lenses (IOL) are also implanted routinely. These pseudophakic procedures have significantly reduced the numbers of patients developing glaucoma after cataract surgery. Implanting an IOL probably protects the anterior segment from some “chemical poison” originating in the posterior segment. (Levin AV. Aphakic glaucoma: a never-ending story? Br J Ophthalmol. 2007 Dec;91(12):1574-5. doi: 10.1136/bjo.2007.121020)

This scenario was not so common about 30 years back when intra-capsular cataract extraction (ICCE) was done in camp surgeries on a mass scale. Such patients were left aphakic and had higher prevalence of aphakic glaucoma. Even the later use of anterior chamber IOLs such as the Choyce Mark VIII did not significantly reduce the number of patients developing glaucoma. The advent of extra-capsular cataract extraction (ECCE) and phacoemulsification has decreased appreciably the incidence of this condition in adult populations. Aphakia increases the risk for suprachoroidal hemorrhage. 

VISUAL FIELD CONSIDERATIONS IN APHAKIA:

Assessment of the visual fields in aphakic glaucoma patients is difficult due to the refractive aberrations in these patients. Contact lenses, both soft and rigid types, can be used in these patients. These lenses reduce the chance of a "lens artifact" affecting the visual field report. Conversely, they increase the total field size visible to the patient, have better blind spot size and plotting and less distortion secondary to prismatic effects.

PEDIATRIC APHAKIC GLAUCOMA:

Currently pediatric cataract surgery is usually associated with aphakic glaucoma. In pediatric patients the posterior capsule is partially or completely removed. This is so since primary posterior capsulotomy is often done in pediatric patients, or the entire lens with its capsules removed in lensectomy procedures. These aphakic children are at increased risk of developing aphakic glaucoma.

Aphakic or pseudophakic glaucoma is the 2nd most common type of childhood glaucoma (after primary congenital glaucoma). The prevalence of pediatric aphakic glaucoma ranges from 4-to-41%.

The factors associated with increased risk of glaucoma following cataract surgery includes surgery in the first year of life, microphthalmia and coexistence of persistence of fetal vasculature.

Scheie and Ewing have defined “early” aphakic glaucoma as that occurring within the first 6 postoperative weeks and “late” aphakic glaucoma as occurring at any later time. (Scheie HG, Ewing MQ. Aphakic glaucoma. Transactions of the Ophthalmological Societies of the United Kingdom. 1978 Apr;98(1):111-117. PMID: 373170.)

The number of patients developing aphakic glaucoma ranges widely, depending upon the time period of the study.

A study to evaluate glaucoma related adverse events in the Infant Aphakia Treatment Study found 9% of 114 patients developing aphakic glaucoma, while 4% were glaucoma suspects. (Beck AD, Freedman SF, Lynn MJ, et al. Glaucoma-Related Adverse Events in the Infant Aphakia Treatment Study: 1-Year Results. Arch Ophthalmol. 2012;130(3):300–305). 

But, a study from Ireland reported 33% patients operated for congenital cataract developing glaucoma in the first year of follow-up. (Kirwan C, Lanigan B, O'Keefe M. Glaucoma in aphakic and pseudophakic eyes following surgery for congenital cataract in the first year of life. Acta Ophthalmol. 2010 Feb;88(1):53-9).

A study by Agarwal et al (1981) from India reported 26.7% eyes developing aphakic glaucoma. Kessing and Rasmussen (1977) had found 1.8% eyes undergoing “microsurgery for senile cataract” developing aphakic glaucoma.

The incidence of aphakic glaucoma increases with the duration of follow-up. It can occur weeks to years after surgery.

A number of factors have been identified with the development of aphakic glaucoma in pediatric patients. These include:

Onset and mechanism of glaucoma= The onset of glaucoma often shows a bimodal pattern of distribution. Aphakic glaucoma with an angle-closure mechanism frequently occurs within the first few months after surgery and open-angle glaucoma has a later onset (average 7.4 years). The longer the patients are followed after cataract surgery, the longer the time for onset of open-angle glaucoma. Children who have undergone cataract surgery have a continuing risk to develop glaucoma throughout their lives.

Timing and role of cataract surgery in glaucoma development= Cataract surgery within the first year of life has been identified as a risk factor for glaucoma. Early extraction of congenital cataracts is considered to be important to achieve good visual and functional results. However, early surgery increases the risk for glaucoma. Vishwanath et al (Vishwanath M, Cheong-Leen R, Taylor D, Russel-Eggit I, Rahi J . Is early surgery for congenital cataract a risk factor for glaucoma? Br J Opthalmol 2004; 88: 905–910) and also Koc (Koc, F., Kargi, S., Biglan, A. et al. The aetiology in paediatric aphakic glaucoma. Eye 20, 1360–1365 (2006)) have recommended delaying cataract surgery until the infant is 4 weeks old in bilateral cases, for a full-term child.

Microcornea= The prevalence of microcornea among aphakic glaucoma patients is as high as 88.5% to 94%. Smaller eyes and eyes with reduced corneal diameter have a predisposition for angle closure. Koc et al found abnormally thick corneas in a number of their patients. This could account for the misleadingly high IOP in some patients. Microphthalmia is a significant risk factor for aphakic glaucoma (Bruce Shields).

Possible mechanisms for delayed-onset open-angle glaucoma= The surgical removal of it early in life can alter normal development of the filtration angle. Studies have found that there is a relative arrest in the normal development of the filtration angle and the trabecular meshwork in the eyes of aphakic children. (Levin AV)

Barotrauma to the immature angle= In support of this theory is the higher frequency of aphakic glaucoma in children who have their surgery at younger ages. Arguing against this theory is the seemingly equal rate of aphakic glaucoma following pars plana lensectomy.

Goniodysgenesis= Some eyes with aphakic glaucoma have an angle appearance which resembles the angle seen in congenital/infantile glaucoma. Such eyes may even respond to goniotomy. This suggests that these eyes seem to have multiple isolated pathologies such as cataract and glaucoma.

Role of the vitreous= In aphakic patients there is often vitreous disturbance and it enters the angle. It is speculated that the exposure of the angle to vitreous causes permanent changes there, affecting aqueous outflow.

Chemical factors= Rupture of the posterior capsule exposes the anterior segment to certain chemicals which could cause changes in the aqueous outflow pathways. Certain vitreous excitatory amino acids and other factors have been speculated, but there needs to be more research done in this area.

Genetic factors= Aphakic glaucoma in children has been found to have familial tendency. It is often bilateral too, raising the possibility of genetic factors responsible for this condition. Many genes are known to be involved in both cataract and glaucoma, PAX6 being perhaps a paradigm. The complex interaction of gene mutations and polymorphisms continues to be unravelled.

MANAGEMENT OF APHAKIC GLAUCOMA

Aphakic glaucoma is a challenging condition to manage. Depending upon the severity of the condition, it has been managed by medical, laser, surgical and other modalities. Open-angle glaucoma can be attempted by conservative means but angle-closure glaucoma or glaucoma associated with angle anomalies needs surgical intervention.

Medically a number of medications such as miotics, phenylephrine and atropine eyedrops (Agarwal H C, Sood N N, Dayal Y. Aphakic glaucoma. Indian J Ophthalmol 1981;29:221-5.) The advent of newer anti-glaucoma agents has widened our armamentarium to manage aphakic glaucoma.

Laser procedures mentioned in the literature include Argon Laser Trabeculoplasty (ALT) (Agarwal and Sood) and Argon laser photocoagulation of ciliary processes (Lee P. Argon Laser Photocoagulation of the Ciliary Processes in Cases of Aphakic Glaucoma. Arch Ophthalmol. 1979;97(11):2135–2138. doi:10.1001/archopht.1979.01020020453008).

Surgical treatments include goniotomy, cyclodialysis, trabeculotomy and trabeculectomy. Angle procedures have been found to be successful in more than half the patients in one study (Bothun ED, Guo Y, Christiansen SP, Summers CG, Anderson JS, Wright MM, Kramarevsky NY, Lawrence MG. Outcome of angle surgery in children with aphakic glaucoma. J AAPOS. 2010 Jun;14(3):235-9. doi: 10.1016/j.jaapos.2010.01.005. Epub 2010 Mar 11. PMID: 20226703.).

Cyclocryotherapy has also been used for management of aphakic glaucoma. A study to evaluate the role of this modality was performed in 96 eyes of 96 patients of aphakic open-angle glaucoma (AO), aphakic angle-closure glaucoma (ACL). IOP was lowered to less than 21 mmHg in 76% of eyes with AO, 68% of eyes with ACL. Glaucomatous field loss was arrested in 71% of patients with AO and 65% of patients with ACL. (Caprioli J, Strang SL, Spaeth GL, Poryzees EH. Cyclocryotherapy in the treatment of advanced glaucoma. Ophthalmology. 1985 Jul;92(7):947-54. doi: 10.1016/s0161-6420(85)33951-9. PMID: 2410846.)

Perhaps the most commonly performed surgical intervention in aphakic glaucoma currently, is the Ahmed Valve Implantation (Kirwan C, O’Keefe M, Lanigan B & Mahmood U (2005): Ahmed valve drainage implant surgery in the management of pediatric aphakic glaucoma. Br J Ophthalmol 89: 855–858). The advantage of the pediatric sized Ahmed valve has made this technique a procedure of choice in the management of aphakic glaucoma in pediatric patients. In adults also aphakic glaucoma is often intractable and Ahmed Valve has been used with positive outcomes. (Wang, H., Chen, H., Qi, Y. et al. Surgical results of Ahmed valve implantation combined with intravitreal triamcinolone acetonide injection for preventing choroidal detachment. BMC Ophthalmol 15, 13 (2015))

REFRACTIVE CORNEAL SURGERY AND OCULAR HYPERTENSION

 

INTRODUCTION:

There is a world-wide increase in the number of individuals opting for corneal refractive surgery procedures, such as photorefractive keratectomy (PRK) and Laser-Assisted In Situ Keratomileusis (LASIK). Since these patients are started on intense steroid eye-drops in the immediate post-operative period, it is practical to understand the implications of steroid-induced ocular hypertension in this scenario.

RISK OF GLAUCOMA IN MYOPIC PATIENTS :

Myopic patients have a high risk of glaucoma. This is attributed to the thinned out and stretched lamina cribrosa and scleral canal.

Intraocular pressure (IOP) exerts a force on the lamina situated at the scleral canal. The scleral canal, where the lamina is located, represents a relatively weak area in the wall of the globe.

IOP, as a force, can be considered to consist of two vector components. First, there is a posterior force vector compressing the laminar plates or pushing it outwards through the scleral canal. There is a second force vector contributed by the stress in the eye wall which pulls radially on the scleral insertion of the lamina. This latter component contributes, in large part, to the stress within the scleral wall.

LaPlace's equation for a spherical shell relates the pressure and radius to the wall stress:
s = (pi-pc)R/2h

In the equation:
s = stress
(pi-pc) = transmural pressure (or difference between internal and external pressure)
R = radius of sphere
h = thickness of sphere

It follows from LaPlace's equation that, for a given transmural pressure, the larger the radius of the globe (i.e., the greater tile axial length), the greater the wall stress and, hence, the greater the
potential distorting force on the optic nerve.

This may in part, explain why eyes with axial myopia may have increased risk for developing glaucoma.

STEROID INDUCED OCULAR HYPERTENSION FOLLOWING CORNEAL REFRACTIVE SURGERY:

Myopic patients usually undergo corneal refractive surgeries, which involves application of laser to the cornea in order to change the contour of the cornea. In this procedure high power laser energy is delivered to the cornea to ablate it. This causes an inflammatory reaction which needs to be controlled by intensive topical steroids, such as every two-hourly per day.

Looking at the risk of myopic patients to develop glaucoma, it is of practical importance to keenly follow-up these patients for any steroid-induced ocular hypertension.

REFERENCES:

In a study from Iran, myopic PRK was performed on 506 eyes of 269 patients. Preoperatively, spherical equivalent refractive error ranged from −1.00 to −5.00 diopters (D) and cylinder was less than 4 D. 

Ocular hypertension developed in 40 (7.9%) eyes overall, which occurred in 16 eyes (40%) 2–3 weeks postoperatively (mean IOP=23.5±3.0mmHg), in 20 eyes (50%) after 4–6 weeks (mean IOP=25.1±4.2 mmHg) and in 4 eyes (10%) 8–12 weeks following PRK (mean IOP=29.0±3.1 mmHg). There was no correlation between the level of IOP rise and preoperative spherical equivalent refractive error. IOP recovered to normal in all eyes after discontinuation of topical steroids and initiation of anti-glaucoma medications. Mean duration of IOP normalization was 28.5±27.7 (range 7–108) days and no instance of steroid-induced glaucoma was observed in any patient.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589213/

In another study from Hungary, 43 paients developed ocular hypertension following PRK. They were divided into three groups. The first received only timolol, the second timolol and dorzolamide and the third only dorzolamaide. The second group treated with a combination of dorzolamide and timolol had the best ocular hypotensive response.

https://pubmed.ncbi.nlm.nih.gov/11489570/

Steroid induced IOP elevation has been noted by Seiler as well as Machat, occurring in 8 to 32% of treated eyes. Shimizu et al reported the incidence of post-PRK IOP rise (>21mmHg) to be 8.9%. Gartry has reported a post-PRK steroid response of 12% in their series.

Seiler T, Holschbach A, Derse M, Jean B, Genth U. Complications of myopic photorefractive keratectomy with excimer laser. Ophthalmology. 1994;101:153–160.

Machat JJ, Tayfour F. Photorefractive keratectomy for myopia: preliminary results in 147 eyes. Refract Corneal Surg. 1993;9(suppl):S16–S19.

Shimizu K, Amano S, Tanaka S. Photorefractive keratectomy for myopia: One-year follow-up in 97 eyes. Refract Corneal Surg. 1994;10(Suppl):S178–187.

Gartry DS, Kerr Muir MG, Marshall J. Excimer laser photorefractive keratectomy.18-month follow-up. Ophthalmology. 1992;99:1209–1219.

CONCLUSION:

In view of the significant number of patients developing elevated IOP in post-PRK patients, these individuals should be monitored no later than 2 weeks after initiation of corticosteroid treatment.

Javadi recommends substituting potent steroids such as betamethasone with weaker agents with lesser propensity for IOP elevation such as fluorometholone.

HEMORRHAGIC CHOROIDAL DETACHMENT

 

INTRODUCTION

• Hemorrhagic CDs (HCDs) are characterized by accumulation of blood in the suprachoroidal space. This occurs due to rupture of branches of short or long posterior ciliary arteries. Arterial rupture is invariably a consequence of precipitous drop in IOP intra-operatively. While post-operatively factors such as prolonged hypotony and inflammation play a role.
• The clinical severity of HCDs differs in intra-operative vs. post-operative scenarios. Intra-operative HCDs are a medical and surgical emergency due to the high risk of expulsion of the contents of the eye through the incision. Post-operative HCDs usually develop gradually and do not have the risk of expulsion of intra-ocular contents.
• A particular type of HCDs is seen following use of antimetabolites (Mitomycin-C or 5-Flurouracil) in glaucoma filtering surgery. This is apparently due to significant hypotony seen with these medications.

ETIOLOGY

• Severe globe trauma is often associated with hemorrhagic choroidal effusions.
• Sudden globe decompression intra-operatively can cause HCD. This is particularly likely if the eye is affected by glaucoma and surgery is performed in the setting of elevated IOP.
• Prolonged hypotony and inflammation predispose to HCDs. Following glaucoma surgery persistent over-filtration and chronic inflammation leading to aqueous shutdown causes hypotony. This increases the risk for HCDs.
• Systemic hypertension, intraoperative tachycardia, arteriosclerosis, high myopia, increased axial length, aphakia, and glaucoma increase the risk for HCDs. In such patients, elevated IOP pre-operatively or acute intraoperative effusion increases the risk for developing HCD.

DIAGNOSIS

PRESENTATION

• Intra-operatively, the surgeon will visualize an enlarging dark mass masking the red fundus reflex.
• The stretching of ciliary nerves causes acute, severe pain in the patient. This could lead to nausea and vomiting.
• Extrusion of intra-ocular contents can occur.
• Post-operative development of HCDs is characterized by sudden, excruciating pain and immediate loss of vision.
• This pattern of symptoms in the setting of recent glaucoma filtering surgery is nearly pathognomonic.

SIGNS

• The IOP is invariably high in HCDs, unlike serous CDs where it is usually low.
• Appearance of hemorrhagic CDs is grossly similar to serous CDs (four lobed appearance in severe cases). However, hemorrhagic CDs do not transilluminate.
• B-scan ultrasonography can distinguish serous vs. hemorrhagic CD. Serous detachments appear as rounded, peripheral lobes filled with echo-lucent fluid. In contrast, hemorrhagic detachments appear echo-dense. (See figure, above)

MANAGEMENT

MEDICAL: Similar to serous CDs

SURGICAL:

• HCDs invariably require surgical drainage. However, in post-operative cases, especially if the hemorrhage is small, conservative treatment can be opted for.
• Intra-operatively, the incision should be closed as soon as possible. Sometimes, we need thicker sutures such as 4-0 or 5-0 nylon.
• The timing of drainage for HCDs is controversial. Usually, in HCDs due to trauma, surgical drainage is delayed by 10-14 days to allow time for clot lysis, making drainage easier. In HCDs developing following glaucoma surgery, the drainage procedure can be delayed depending on the clinical situation. If there is over-filtration from the bleb, it may have to be revised.
• In cases there is associated retinal detachment, vitreo-retinal traction or vitreous hemorrhage, vitreo-retinal surgery (e.g. PPV) is required.

 

 

SEROUS CHOROIDAL DETACHMENT

 

INTRODUCTION:

• Terms such as choroidal effusion, ciliochoroidal effusion, choroidal detachment, and ciliochoroidal detachment are used for somewhat similar entities and occasionally mentioned interchangeably in the literature.
• However, choroidal detachment is a broader term than choroidal effusion.
• The terms choroidal effusion, ciliochoroidal effusion, and serous choroidal detachment describe the same entity.
• A choroidal detachment (CD) is defined as abnormal presence of fluid or blood in the suprachoroidal space.
• The suprachoroidal space is the potential space between the choroid and the sclera.
• CD is of in two types—serous and haemorrhagic. Serous choroidal detachments, also known as choroidal effusions, are a frequent complication of glaucoma surgery.
• Glaucoma surgery is the most common cause of choroidal detachments, which may occur in 3-34% of trabeculectomies and 3%-35% of glaucoma implant procedures. Newer techniques such as MIGS have lower incidence of CDs.
• Other causes of choroidal detachment include infection (e.g., herpesviruses, human immunodeficiency virus), inflammation (e.g., posterior scleritis, drug-induced cyclitis, Vogt-Koyanagi-Harada syndrome), malignancy (e.g., primary intraocular lymphoma or metastatic carcinoma), or episcleral venous congestion (e.g., Sturge-Weber syndrome, dural arteriovenous fistula.
• Uveal effusion syndrome is a rare cause of idiopathic choroidal effusions that may involve impaired posterior segment drainage and congenital anomaly of the sclera resulting in scleral thickening.
• Following glaucoma surgery hypotony may occur, resulting in pressure-driven osmotic shifts of serous fluid from the choroidal capillaries into the suprachoroidal space due to decreased vascular permeability.
•  Due to the increased use of antimetabolites, there is increased incidence of persistent choroidals, complicating the postoperative course with prolonged visual compromise, shallow anterior chambers, cataract formation, and bleb failure.
• Choroidal effusions further potentiate hypotony due to reduced aqueous humor production.
• Disturbances in the hydrostatic and oncotic pressure gradients and high permeability of the choriocapillaris result in serum or blood accumulation in the suprachoroidal space. This fluid accumulation leads to thickening of the choroid and the formation of a fluid-filled suprachoroidal layer.
• Low IOP or a disruption to uveoscleral outflow also promotes fluid accumulation within the suprachoroidal space.

SEROUS CHOROIDAL DETACHMENTS:

• Serous choroidal effusions result from transudation of serum into the suprachoroidal space.
• Starling’s equation explains the movement of fluid between the plasma and interstitium. According to this equation, the movement is determined by the relative hydrostatic and oncotic pressures of these compartments.
• Drastic fall in IOP such as that occurring following incisional glaucoma surgery allows fluid to accumulate in the interstitial space, due to a higher capillary pressure relative to interstitial pressure.
• Other factors which can contribute to the formation of choroidal effusions include:
• Inflammation-induced increases in choroidal capillary permeability and high hydrostatic pressure in the choroidal vascular plexus secondary to hypertension.
• Accumulation of proteinaceous serum in the suprachoroidal space disturbs the equilibrium between the oncotic pressure in the interstitium and plasma limits uveal resorption.
• These non-resolving choroidal effusions may result in serous retinal detachment due to failure of the retinal pigment epithelium pump mechanism.

RISK FACTORS FOR SEROUS CDs:

SURGERY

Glaucoma filtration surgery (GFS) [e.g., trabeculectomy or MIGS implantation].

Glaucoma Drainage Device (GDD) implantation [especially valved devices].

Laser peripheral iridotomy.

Retinal surgery (pars plana vitrectomy or scleral buckling procedure).

Any glaucoma surgery with intraoperative or postoperative hypotony.

 

OCULAR MEDICATIONS

Antimetabolite (mitomycin C or 5-fluorouracil) augmented GFS especially in the setting of prolonged hypotony.

Topical aqueous suppressants (e.g., timolol and dorzolamide) after trabeculectomy or GDD implantation.

Topical prostaglandin analogs (e.g., latanoprost, travoprost, and bimatoprost) have been associated with late choroidal effusions following cataract extraction or GFS.

Intravitreal injection of ocriplasmin has also been reported as a cause of choroidal effusion.

 

SYSTEMIC MEDICATIONS

Carbonic anhydrase inhibitors.

Anticoagulants.

Topiramate.

Tamsulosin.

Sulfonamides (e.g., chlorthalidone, sulfamethoxazole-trimethoprim, indapamide)

Antidepressants (e.g., escitalopram, venlafaxine, bupropion)

Angiotensin receptor blockers (e.g., losartan)

Chemotherapeutics (e.g., docetaxol and gemcitabine)

Pergolide (a dopamine agonist used to treat Parkinson’s disease)

Drugs of abuse (e.g., 3,4-methylenedioxymethamphetamine a.k.a. “ecstasy” or MDMA)

 

PRE-EXISTING CONDITIONS

Nanophthalmos

Sturge-Weber syndrome

Hypermetropia

Systemic hypertension

Atherosclerosis

Diabetes mellitus

Prior cataract surgery

Glaucoma

Diffuse choroidal hemangioma

Older age

History of choroidal detachment in the other eye

 

TREATMENT-RELATED FACTORS 

Lower postoperative IOP

Full-thickness filtration surgery

Ocular inflammation

Aqueous suppressant therapy

 

PRIMARY PREVENTION OF CDs:

• Acute glaucoma surgery-related CDs may be prevented by minimizing hypotony, bleeding, and inflammation intra-operatively and post-operatively.
• Pre-operative medications (Carbonic anhydrase inhibitors or osmotic agents) can be used to reduce IOP.
• Intra-operative proper and meticulous surgical technique would avoid the development of CDs.
• The scleral flap should be constructed at 50-75% scleral depth.
• To prevent early hypotony, multiple sutures can be placed in the scleral flap.
• Suture release should be delayed by at least one week.
• A stable anterior chamber can be achieved with a cohesive ophthalmic viscosurgical device or anterior chamber maintainer.
• Antimetabolites should be used carefully, as their use can increase the risk of CD.
• When non-valved GDDs are implanted, the tube should be ligated with dissolvable polyglactin suture intra-operatively, or two-stage surgery should be performed with the tube remaining in the subconjunctival space outside the eye and being placed into the anterior chamber at a later time.
• Proper water-tight closure of the conjunctiva should be done at the end of the surgery (it can be confirmed by placing a fluorescein strip over the conjunctival wound and doing the Seidel’s test)
• Releasable sutures and restrictive devices may be used to reduce hypotony, but these tools do not prevent choroidal detachment completely.
• Post-operative care: Topical and systemic aqueous suppressants should be discontinued post-operatively, and early laser suture lysis should be avoided.

DIAGNOSIS:

• Post-operative CDs develop around 2-5 days after surgery.
• Small, peripheral effusions are asymptomatic and usually resolve spontaneously.
• Large effusions affect peripheral vision and may occasionally be large enough to obstruct the visual axis.
• Anterior displacement of the lens-iris diaphragm causes a myopic shift and results in secondary angle closure. Appositional choroidal detachments, which extend from the optic nerve to the lens, are more likely to obscure central vision and cause secondary angle closure.
• Young patients are more prone to develop hypotonic maculopathy.
• Persistent hypotonic maculopathy leads to permanent vision loss.

SIGNS & INVESTIGATIONS:

• The AC can be of normal depth, shallow, or flat.
• AC shallowing is typically diffuse, as pressure from choroidal swelling is indirectly transmitted to the posterior surface of the lens via the vitreous body.
• IOP can be normal, low, or elevated in the setting of choroidal detachment. Typically, low IOP accompanies serous choroidal detachments.
• Fundus examination reveals a multi-lobed appearance. Up to four smooth lobes may be visualized, extending to the vortex veins.
• The fluid-filled lobes of serous detachments demonstrate transillumination. Conversely, hemorrhagic detachments do not transilluminate. Choroidal detachments can be distinguished from retinal detachments based on their more anterior location, extension to the ora serrata, and unique morphology resulting from the choroid’s strong attachments at the sites of the vortex veins.
• B-scan ultrasonography can distinguish serous vs. hemorrhagic CD. Serous detachments appear as rounded, peripheral lobes filled with echo-lucent fluid.
• Ultrasound biomicroscopy (UBM) can be used to visualize anterior rotation of the ciliary body associated with CDs.
• UBM can serve a helpful diagnostic role in confusing cases, as it can distinguish secondary angle closure due to choroidal effusions or a choroidal tumor from a pupillary block angle-closure mechanism.
• Occasionally, wide field fundus photography and swept source optical coherence tomography can also be used to detect and monitor choroidal detachments, with improved detection of peripheral CD.

DIFFERENTIAL DIAGNOSIS:

Retinal detachment

Choroiditis

Central serous chorioretinopathy

Choroidal melanoma

Uveal effusion syndrome

Idiopathic ciliochoroidal effusion

Pseudophakic or aphakic pupillary block

Malignant glaucoma

 

MANAGEMENT:

MEDICAL MANAGEMENT

Most CDs resolve spontaneously. Surgical interventions have been found to cause more visual worsening compared to conservative/medical treatment.

Initially, CDs can be treated with steroids and long-acting cycloplegics such as atropine and cyclopentolate).

Topical steroids are used in an effort to increase IOP and control any inflammation which may be contributing to CD. In severe cases that are refractory to topical medications, systemic steroids may be used.

Any medications promoting ocular inflammation should be discontinued.

SURGICAL MANAGEMENT

In case of wound leaks, a bandage contact lens or suture(s) placed with a tapered (blood vessel) needle can be used to close leaking areas, if the AC is still formed and deep.

If there is an over-filtrating trabeculectomy, transconjunctival sutures may be placed using a tapering needle to secure the scleral flap.

The AC can be reformed by inserting a cohesive or ultracohesive viscoelastic material (e.g., Healon 5 or Healon GV, respectively) through the already-formed intraoperative paracentesis track. In some instances, multiple viscoelastic injections may be necessary to maintain AC depth and IOP.

Injections are performed under topical anesthesia, and IOP should be measured afterward to monitor for ocular hypertension due to over-installation of viscoelastic.

SURGICAL DRAINAGE OF CHOROIDAL DETACHMENTS IS INDICATED IN THE FOLLOWING CASES

Flat anterior chamber

Persistent corneal edema with a shallow anterior chamber

Significant eye pain

Elevated IOP refractory to medical management

Longstanding choroidal effusion

Appositional choroidal effusion and/or apposition of the central retina

Hemorrhagic choroidal detachment

Decreased vision

 

• Drainage procedures involve deepening the AC while choroidal fluid egresses out of a full-thickness scleral incision behind the limbus.
• First, a tangential conjunctival incision is made 3-6 mm from the limbus in the quadrant where the effusion is most substantial; a 2-3 mm radial sclerectomy is then placed 3-4 mm posterior to the limbus.
• Choroidal fluid egresses spontaneously and/or with assistance by holding the incision open with forceps or gently depressing the adjacent sclera with a cyclodialysis spatula.
• Finally, the AC is deepened by injecting saline solution via a paracentesis incision.
• This procedure has a reported 77% success rate by 12 months follow-up, defined as complete resolution of the choroidal detachment, normalization of anterior chamber depth, and resolution of hypotony. Most patients had improved visual acuity as well.
• Cataract extraction is part of treating CD. When a visually significant cataract is present in combination with CD, then combined cataract extraction and CD drainage should be performed. Cataract extraction may be considered for non-resolving choroidal detachment, as this may in some cases result in resolution.

PROGNOSIS:

Serous choroidal effusions are usually benign and do not significantly reduce visual acuity.

A large, persistent effusion, however, may cause significant morbidity, particularly when it is associated with hypotony maculopathy or serous retinal detachment.