SAFFRON AND GLAUCOMA

 

Introduction

Abnormal resistance to the outflow of aqueous humor through the trabecular meshwork (TM) is a key factor in the pathogenesis of primary open angle glaucoma (POAG).

Oxidative stress plays a role in the development of POAG by causing changes in the TM.

Saffron is derived from the pistils of Crocus sativus.

It contains high concentration of crocin and crocetin (carotenoid derivatives).

Saffron is a powerful radical scavenging, antioxidant and antitumor agent.

In a study performed in Iran, it has been shown that high doses of oral saffron extract can reduce intra-ocular pressure (IOP).

The saffron study

The above mentioned study was performed at the 22nd of Bahman Hospital, Gonabad, Iran.

Inclusion criteria were set as: Patients with POAG older than 50 years of age being treated with timolol 0.5% BD and Dorzolamide 2% TID, judged to have stable glaucoma control for atleast 6 months, based on a series of visual field and optic nerve head examinations.

34 patients were randomized to receive either saffron extract or placebo.

The study was kept double blinded from patients, ophthalmologists and statisticians.

Crocus sativus stigmas were collected from Gonabad. Using the maceration technique saffron capsules containing 30 mg of concentrated powder was prepared. Starch powder capsules were used for placebo.

Subjects were randomly assigned to oral saffron (30mg per day) or oral starch capsules for one month, while continuing the topical medications.

At the end of the study all patients entered a one month washout period when saffron was stopped while continuing the topical medications.

Results: Mean baseline IOP was 12.9+/- 3.7 (7-19) mmHg in the saffron group and 14+/-2.5 (9-18) mmHg in the control group.

One week after intervention, IOP was 12+/-3.3 mmHg in saffron group vs. 13.6+/-2.6 mmHg in the control group. At four weeks IOP was 10.6+/-3 (6-16) mmHg in saffron group vs. 13.8+/-2.2 mmHg in control group. At the end of the washout period IOP was 12.9+/-3 (8-18) mmHg in saffron group and 14.2+/-2.0 in the control group.

Discussion

Antioxidants are beneficial in reducing the risk of multiple ocular diseases including AMD.

Oxidative stress is also implicated in the development and progression of POAG.

The trabecular meshwork is especially sensitive to oxidative stress.

Light-induced formation of oxidative radicals may target the TM and contribute to the pathogenesis of glaucoma.

Disturbed cell homeostasis from oxidative stress may lead to cellular loss and structural alterations in it's extracellular matrix, resulting in impaired aqueous humor outflow and thereby an increase in IOP.

Saffron has the ability to reduce IOP, but it may also have antioxidant-neuroprotective properties.

Antioxidants exert a short term effect by rehabilitating damaged but still functional TM, and a long-term benefit by reducing apoptosis.

The ocular hypotensive effect shown by saffron extract can be attributed to short term effect.

Safety

Saffron has low toxicity and doses upto 1.5gm are regarded as safe.

The colored constituents of saffron may accumulate in sclera, skin and other tissues to mimic icteric features.

Nausea, vomiting, diarrhea is reported in doses around 1.5-2gm.

Conclusion

 Saffron may prove to be a safe and effective hypotensive agent with additional antioxidant-neuroprotective properties.

1st Ocular Blood Flow Summit

 The first Ocular Blood Flow Summit was organized in Rigi Kaltbad, Switzerland, under the Chairmanship of Prof Josef Flammer.

Here are some impressions of the Summit.

NEOVASCULAR GLAUCOMA

ZAKIYA KHATOON

Ajmal Khan Tibbiya College

Aligarh, India

AHMED GLAUCOMA VALVE

Guest author

TANZEELA KHAN

Ajmal Khan Tibbiya College

Aligarh, India

INTRODUCTION

• Intraocular pressure (IOP) is the main risk factor for the development and progression of glaucoma.
• IOP reduction can be achieved by medical, laser or surgical therapy.
• Glaucoma filtration surgeries have high success rates during the early years (70-90%) but the effects tend to decrease with time.
• The success of trabeculectomy is largely influenced by the healing process in the anterior subconjunctival space.
• Aqueous shunts (also called Glaucoma Drainage Devices [GDDs]) are a reliable alternative to trabeculectomy.
• By shunting aqueous to the posterior subconjunctival space these devices may avoid healing issues, especially in patients who have already undergone previous glaucoma surgeries or conjunctival manipulation.
• Ahmed Glaucoma Valve (AGV) is a highly successful GDD which has been implanted in thousands of individuals world-wide.

AGV: DEVICE DESCRIPTION AND TECHNICAL DATA

• AGV provides a complex mechanism to control aqueous humor outflow.
• The device was developed by Dr Abdul Mateen Ahmed, a biomedical engineer of Indian descent.

• The AGV consists of 3 parts:

1. Plate (made of medical grade silicone, polypropylene or porous polyethylene, depending upon the model).
2. Drainage tube (made of silicone).
3. Valve mechanism (made of silicone).

• The adult model (S2) of AGV provides 180 mm² of total plate area.
• The pediatric model (S3) has a total plate area of 96 mm².
• A variant with 2 plates (total filtration area= 360 mm²) and one with a clip for pars plana tube insertion have also been designed.
• The M4 model is made of porous high-density polyethylene (Medpor).
• The valve mechanism of AGV consists of thin silicone elastomer membranes, which are 8 mm long and 7 mm wide and create a Venturi-shaped chamber.
• The membranes open and close in response to IOP variations over a range of 8-12 mmHg.
• After implantation aqueous humor flows slowly and continuously into the trapezoidal chamber of the valve.
• As the pressure reaches the reset threshold value, the valve opens, thus decreasing IOP.
• Since the inlet cross-section of the chamber is wider than the outlet, a pressure differential is created across the chamber.
• This pressure differential enables the valve to remain open even with a small pressure differential between the anterior chamber and subconjunctival spaces surrounding the device.
• AGV complies to Bernoulli’s equation (fluid flowing into section A= fluid flowing out of section B) by increase in fluid velocity as it leaves the chamber through the drainage tube.
• The increased velocity and non-obtrusive flow account for better evacuation and smaller valve friction.
• The tension in the silicone membranes helps to reduce hypotony by closing after the pressure has decreased to normal again.

Mechanism of action of the AGV

SURGICAL TECHNIQUE

• The AGV is primed prior to implantation by injecting 1 cc of balanced salt solution.
• A fornix or limbus based conjunctival flap is fashioned.
• Usually the supero-temporal quadrant between the superior and lateral recti muscles is used.
• The body of the implant is positioned 8-10 mm from the limbus.
• The plate is sutured to the sclera by 9-0 or 10-0 nylon sutures.
• The drainage tube is trimmed so that 2-3 mm enters the AC. The tip is cut at a bevel of 30 degrees to facilitate insertion.
• The AC is entered 2-3 mm behind the corneo-scleral limbus.
• In patients with previous vitrectomy, the tube is inserted into the vitreous and fixed to the sclera by a pars plana clip.
• The drainage tube is covered with preserved donor sclera, pericardium, cornea or any other suitable patch graft material.
• Alternatively a 2/3rd thickness scleral flap is created, a needle tract is made and the tube inserted through this passage.
• The flap should be securely sutured to prevent aqueous egress from around the tube.
• Recently fibrin glue has been used to paste the scleral or bovine pericardial graft over the tube.
• The use of antimetabolites in AGV implantation is debatable. There are studies which do not show any significant difference when compared with no antimetabolite use. Others have reported good success rates when intra-operative MMC and post-operative 5-FU were used.

COMPLICATIONS:

1. HYPOTONY:

In the Ahmed versus Baerveldt (AVB) Study 6.1% patients in the Baerveldt group experienced vision threatening complications related to hypotony at 3 year analysis while none in the Ahmed valve group had similar complications.

In the Ahmed-Baerveldt Comparison (ABC) study, 1 eye (2%) in AGV group had persistent hypotony, compared to 6 eyes (13%) in the Baerveldt group at 5 years of follow-up.

2. IOP INCREASE AND EXCESSIVE CAPSULAR FIBROSIS:

The hypertensive phase after AGV implantation is quite common, peaking at 1-3 months post-operatively and resolving within 6 months. It is probably less common in those with silicone AGV implantation compared to polypropylene. Primary reason for IOP increase is from capsular fibrosis.

Digital massage is an option for the management of the hypertensive phase. If the IOP rises later than 6 months, capsular fibrosis and encapsulation of the plate is evident, then needling may resolve the situation.

3. TUBAL EXPOSURE:

Tubal exposure is reported in 5-14% patients. It can lead to inflammation, hypotony, poor vision and late endophthalmitis. In a study of AGV and Baerveldt implants, no significant differences in tubal exposure rates were found between the two devices. Younger age, prior inflammation and inferior quadrant implantation were significant risk factors for development of tube exposure.

4. CORNEAL COMPLICATIONS:

Silicone tubes in the AC can disturb the corneal endothelium and induce corneal decompensation. Long term frequency of this complication is reportedly 9-27%.

In the AVB study, corneal edema was present in 7% patients of the AGV group and 14% patients in the Baerveldt group at 3 years of follow-up.

Risk factors such as high IOP, long duration of high IOP, toxicity of preservative in the eyedrops and duration of surgery play a part in corneal decompensation.

5. INFECTION AND ENDOPHTHALMITIS:

It is a rare complication following GDD implantation. In a study conducted in Saudi Arabia (1994-2003), out of 542 implantations, 9 developed endophthalmitis (5 cases being in pediatric age group).

Younger age and conjunctival erosion over the tube are significant risk factors for the development of endophthalmitis. The exposed tube may act as a direct channel for intraocular passage of conjunctival flora from the ocular surface.

6. DIPLOPIA AND STRABISMUS:

Diplopia and strabismus are well known post-surgical complications of GDD implantation. Patients with Baerveldt device implantation have the highest rates of these complications. The cause of diplopia is likely restrictive strabismus, either from the plate itself or from plate impinging on muscle insertion.

ExPress Mini Shunt

Guest author

ANAM TARIQ

Ajmal Khan Tibbiya College

Aligarh, India

The ExPress Mini Glaucoma Shunt diverts aqueous from the anterior chamber to a subconjunctival reservoir without removal of scleral or iris tissue.

Background:

The ExPress Mini Glaucoma shunt was originally developed by Optonol Ltd for implantation under the conjunctiva for controlling intra-ocular pressure (IOP).

This biocompatible device is almost 3 mm long with an external diameter of approximately 400 microns. It is non-valved, MRI compatible, stainless steel device with a 50 microns lumen. 

It has an external disc at one end and a spur like extension on the other to prevent extrusion.

The unguarded technique of implantation under the conjunctiva caused various complications, such as:

• Hypotony
• Erosion
• Extrusion of implant
• Endophthalmitis

To avoid these complications, implantation under the scleral flap is being performed.

Surgical technique:

Topical or retrobulbar anesthesia is administered depending on patient selection and surgeon preference.

Step 1: A standard fornix or limbal based conjunctival incision is performed to gain exposure to scleral bed adjacent to the limbus. Gentle cautery is performed in this area.

Step 2: A scleral flap is created in a manner similar to what is performed in a standard trabeculectomy.

Care is taken to direct the flap upto clear cornea.

Anti-fibrotic agents can be applied either before or after the creation of the scleral flap in the usual manner based on the surgeon's preference.

Step 3: A temporal paracentesis is created through the cornea.

The scleral flap is lifted and care is taken to identify the centre of the "blue line" adjacent to the clear cornea which corresponds to the location of the trabecular meshwork.

A 26-gauge needle is inserted into the anterior chamber through the centre of the "blue line" at an angle parallel to the Iris plane. Any lateral movement of the needle, especially when removing, should be avoided as this will cause aqueous to flow around the implant.

Step 4: The ExPress Mini shunt is preloaded on an injector. Fitted into the lumen of the shunt is a metal rod that is attached to the end of the injector.

The shunt is then placed in the anterior chamber through the ostium created with the needle. The angle of the entry with the shunt is the same as the angle used to make the ostium. The shunt is inserted all the way into the wound the plate flush with the scleral bed.

In some procedures standard punctal plug inserter, the injector has an area on the shaft that is depressed which retracts the metal rod in the lumen of the shunt.

Step 5: The scleral flap is then sutured in place using 10-0 nylon suture on a spatulated needle. One to three sutures are typically required depending on the flow which can be tested by inflating the anterior chamber with balanced salt solution using a 27 or 30 gauge cannula through the temporal paracentesis.

Step 6: The conjunctiva is then meticulously closed with the surgeon's suture of choice.

Relative contraindications:

Congenital and juvenile glaucoma, aniridia and anterior segment dysgenesis, phakic primary angle closure glaucoma, pseudophakic glaucoma with an anterior chamber intra-ocular lens, neovascular glaucoma, patients with thin sclera.

Absolute contraindications:

• Acute attack of angle-closure glaucoma.
• Microphthalmia.
• Nanophtalmos.

Complications:

1. Early postoperative high IOP: Due to overfilling of anterior chamber with viscoelastic. Only 1/3rd of anterior chamber should be filled with viscoelastic.

2. Early postoperative hypotony, loss of anterior chamber depth and choroidal detachment: Overfiltration can be avoided by a large securely sutured scleral flap. In case of implant-iris touch the AC can be filled with viscoelastic or a pressure bandage/ double padding/ Simmon's shell can be used.

3. Implant-iris touch: A misplaced incision which is not parallel to the Iris can lead to implant-iris touch. In cases of significant Iris indentation by the ExPress shunt, especially phakic patients, the device should be repositioned. The shunt is explanted, a new track made and the implant re-inserted. In order to facilitate removal of the ExPress Mini shunt it should be rotated so that the spur becomes horizontal, the wound enlarged by a 15' blade and the implanted removed.

4. Extrusion of implant: This can occur spontaneously or following trauma.

5. Malposition of ExPress shunt and it's consequences: A malpositioned implant can erode the conjunctiva. That is also an indication for repositioning of the shunt.

6. Long term corneal endothelial cell loss: Anterior implantation of the shunt can cause endothelial cell damage especially in the superior cornea.

7. Infection: Use of Antimetabolites increases the risk of infection. However, it is not clear whether the device should be removed if endophthalmitis ensues.

8. MRI safety: The patients can undergo MRI scans 2 weeks after implantation and withstand upto 3 Tesla. However, it is not known what will be effects if more than 3 Tesla are required/used.

9. Economic consideration: The cost of the device (Rs 33,000 in India. Approximately 465 USD) is too high for most self-paying patients and this premium cost may itself put unrealistically high expectations regarding the success of the procedure in the patients.