Ophthalmology Update

OPHTHALMIC UPDATES    VOL 10   AUG 11

Antioxidants in the Prevention and Treatment of Diabetic Retinopathy – A Review

Diabetes Mellitus affects more than 230 million people worldwide, and this number is expected to reach 350 million by 2025. Globally the affected people are unaware of the disease and only half receive adequate treatment. It is therefore not surprising that diabetic retinopathy (DR) is the leading cause of blindness in people aged 25- 74 years worldwide. Recently, much attention has been focused on the role of Oxidative Stress, and has been suggested that this may constitute the cause of different pathogenesis in diabetic complications, such as DR.

In diabetes, the retina exhibit increased OS since the eye is constantly subjected to light irradiation, atmospheric oxygen, environmental chemicals, and physical abrasion. The retina has also a natural high content of (PUFA) and possess the highest oxygen uptake and glucose oxidation relative to any other tissue, which makes it more susceptible to OS than other organs or structures.

In retinopathy, OS has been widely involved in decreased retinal blood flow, increased vascular permeability, disruption of BRB and the appearance of acellular capillaries from the apoptotic loss of retinal capillary cells. OS has also been linked to microvascular abnormalities in DR, degenerative process of retinal neovascularization, and the suppression of antioxidants systems. Further, increased OS has been shown to play a critical role in AGEs products-induced apoptosis of retinal capillary cells. ROS can indirectly induce apoptosis by changing cellular redox potentials, depleting GSH and reducing ATP levels. The release of ROS also increases mitochondrial pore permeability that in turn triggers the release of cytochrome c and other proapoptotic factors from retinal mitochondria, initiating apoptosis via activation of caspases and increased cytochrome c is observed in the retina and its capillary cells in diabetes.

It is worthy to mention the various factors related to DR and underline the prominent importance of OS in the development and progression of DR. Several diabetes-induced abnormalities in the retina that are postulated in the development of retinopathy are influenced by OS and are considered to be interrelated.

Dietary supplementation with antioxidants has been related with inhibition of diabetes-induced abnormalities of retinal metabolism, reduction of apoptosis and partial restoration of pericytes.

Ocular antioxidant potential therapy represents a non-invasive, safe and less painful methodology, which slows the natural progress of the disease and improves the effectiveness of treatment without significant systemic toxicity.

Journal of Diabetes and Metabolism   Published December 09, 2010

In the Carotenoids and Co-Antioxidants in Age-Related Maculopathy (CARMA) study, investigators examined the effects of supplementation with serum lutein and zeaxanthin to coantioxidants (vitamins C and E and zinc), compared with placebo, on visual function and progression from early to late stages of AMD. Investigative team member Usha Chakravarthy, MD, PhD, from Queens University of Belfast in Northern Ireland, presented the results.

A total of 433 patients (with early AMD features in at least 1 eye, or any level of AMD in the study eye and late-stage AMD in the fellow eye) were enrolled in 2 centers in the United Kingdom (1 in Belfast and 1 in Waterford). The patients were randomized to receive either carotenoids plus coantioxidants (C+CA; n = 216) or placebo (n = 217).

The primary outcome was BC DVA as measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at 4 meters at 12 months. Secondary outcomes included improved or preserved interferometric acuity, contrast sensitivity, shape discrimination ability, Raman spectroscopy for macular pigment, and change in AMD severity as monitored by fundus photography by trained readers.

At every study visit (baseline and at 12, 18, 24, 30, and 36 months), fundus photographs were graded, and serum lutein, zeaxanthin, and the other antioxidants were measured. An analysis of covariance adjusted for baseline covariates was performed at 12 months.

Results at 36 Months Significant

Results from this study showed that although the mean change in BC DVA at 12 months favored the C+CA group (0.002 in the C+CA group vs 0.007 in the placebo group), the difference was not statistically significant (P = 0.5). Stronger differences were found in the study's later stages, especially at the 36-month mark.

However, as the trial went on, the number of participants in the C+CA and placebo groups dropped significantly because of self withdrawal: at 18 months, there were 122 and 126 participants, respectively; at 24 months, 92 and 95; at 30 months, 58 and 52; and at 36 months, 21 and 20.

"There was a steady increase in the differential change in best corrected visual acuity between treatment groups," explained Dr. Chakravarthy. "At the 36-month follow-up, BC DVA was better in the treated eyes, and statistically significant, In addition, a 10-fold increase in serum lutein was associated with a 4-letter improvement in DVA (B –0.77, t –2.42; = .017), and a higher serum lutein was associated with a slower rate of AMD progression (= .011).

"In conclusion, the CARMA study suggests that supplementation with lutein and zeaxanthin results in better macular function in patients with early AMD," said Dr. Chakravarthy. "And as the eyes of persons who had high serum [lutein] demonstrated a less severe early AMD change over time, supplementation may prove beneficial in preventing progression to late AMD.

Association for Research in Vision and Ophthalmology (ARVO) 2009 Annual Meeting: Abstract 1257. Presented May 4, 2009.  Fort Lauderdale, Florida

Pre-seasonal treatment with topical olopatadine suppresses the clinical symptoms of seasonal allergic conjunctivitis.

PURPOSE:

To evaluate the effectiveness of pre-seasonal treatment with topical olopatadine on the reduction of clinical symptoms of seasonal allergic conjunctivitis (SAC).

DESIGN:

Prospective interventional case series.

METHODS:

Eleven patients with SAC received topical olopatadine in one eye at least two weeks before the onset of allergy symptoms, and the other eye served as the control. After the onset of allergic conjunctivitis, both eyes were treated with topical olopatadine. Visual analogue scale (VAS), which evaluated the subjective symptoms of ocular allergy, and the tear levels of histamine and substance P were measured up to six weeks.

RESULTS:

At the onset of allergy symptoms, the VAS score in the pretreatment eyes was statistically significantly lower than that in the control eyes. The VAS score in the control eyes decreased with time but did not decrease to the level seen in the pretreatment eyes until four weeks later. The tear level of substance P at the onset of allergy symptoms was significantly suppressed in the pretreatment eyes, while the level of histamine was not suppressed. Alteration of the VAS scores in the pretreatment eyes significantly correlated with the level of substance P, but not of histamine.

CONCLUSIONS:

To suppress clinical symptoms in patients with SAC, pre-seasonal treatment with topical olopatadine is effective. The effectiveness of treatment correlates with the tear level of substance P.  

Am J Ophthalmol.2011 Apr;151(4):697-702.e2. Epub 2011 Jan 22.

 

Olopatadine: a drug for allergic conjunctivitis targeting the mast cell.

IMPORTANCE OF THE FIELD:

Ocular allergic diseases are characterized by specific activation of conjunctival mast cells with subsequent release of preformed and newly formed mediators. Mast cells are thus the first therapeutic target of ocular anti-allergic treatments.

AREAS COVERED IN THIS REVIEW:

In this review, a Medline literature search was conducted on conjunctival mast cells, their role in ocular allergy and mast cell stabilization by ocular anti-allergic compounds.

WHAT THE READER WILL GAIN:

Olopatadine hydrochloride, a mast cell stabilizer and histamine receptor antagonist, has been shown to inhibit mast cell activation in an in vitro model of human mast cell culture, reducing histamine and TNF-alpha release and upregulating proinflammatory mediators in conjunctival epithelial cells. In the in vivo conjunctival allergen challenge (CAC) model in allergic subjects, combined with objective evaluations of tear mediators and cytology, olopatadine reduced histamine tear levels and all aspects of allergic inflammation, confirming the positive clinical effects observed in active allergic patients.

TAKE HOME MESSAGE:

Mast cells play a central role in the pathogenesis of ocular allergy. The CAC model is ideal for assessing the mast cell stabilizing effects of anti-allergic compounds. This review of clinical studies demonstrates the superiority of olopatadine compared with other topical allergic drugs.

Expert Opin Pharmacother.2010 Apr;11(6):969-81.

Medicated contact lenses could do away with drops

Contact lenses which release drugs directly into the eye could soon be used to treat common eye diseases.

Scientists have developed soft contact lenses which can ' dispense' prescription drugs over a period of weeks to the exact spot they are needed.

The disposable lenses - which are embedded with tiny particles of medicine - will be effective against glaucoma, infections and other eye complaints, according to researchers at the University of Florida.

The lenses also promise to be far more efficient than eye drops, the method currently used to clear up such complaints.

Assistant Professor Anuj Chauhan, the study's author, said: 'One of the biggest problems with using eye drops to deliver medication to the eyes is that about 95 per cent of the medication goes where it's not needed.'

He said traditional eye drops mix with tears, which then drain into the nasal cavity and get into the bloodstream, where the drugs can cause serious side effects.

For example, Timolol, used to treat glaucoma, can cause heart problems.

But drugs contained in a contact lens can be released slowly enough to stay in the eye.

Making a presentation at today's meeting of the American Chemical Society in New Orleans, the scientists will reveal they have found a way to encapsulate a drug in nanoparticles - tiny particles much smaller than the eye can see - which are then mixed into the contact lens's 'raw materials' during manufacture.

In theory, the disposable, drug-laden contact lenses could be worn for up to two weeks, delivering a steady supply of medication directly to the eye.

Mail Online        www.dailymail.co.uk   30th June 2011

Intraocular Oxygen Distribution in Advanced Proliferative Diabetic Retinopathy

Purpose

To determine the preretinal distribution of oxygen in advanced proliferative diabetic retinopathy, and to investigate the relationship between intraocular oxygen tensions and vitreous cytokine concentrations.

Design

Comparative cross-sectional study.

Methods

Oxygen levels were measured at sites in the vitreous and at the inner retinal surface using an optical oxygen sensor in 14 control subjects and in 14 subjects with advanced proliferative diabetic retinopathy who had developed tractional retinal detachments despite previous panretinal photocoagulation. The vitreous and plasma concentrations of 42 cytokines were measured using multiplex cytokine arrays and their correlation with intraocular oxygen tension was investigated.

Results

The mean oxygen tension in the mid-vitreous in diabetic retinopathy was 46% lower than that in control subjects (P = .017). However, the mean preretinal oxygen tension at the posterior pole in diabetic retinopathy was 37% higher than in controls (P = .039). We measured significant alterations in the vitreous concentrations of 9 cytokines—eotaxin, Flt-3 ligand, growth-related oncogene (GRO), interleukin (IL)-6, IL-8, IL-9, IFN-inducible protein-10 (IP-10), macrophage-derived cytokine (MDC), and vascular endothelial growth factor (VEGF)—in advanced proliferative diabetic retinopathy, and found that oxygen tension at the posterior pole was directly correlated with vitreous VEGF concentration.

Conclusion

We identified significant intraocular oxygen gradients in proliferative diabetic retinopathy. Our findings are consistent with the hypothesis that VEGF induces the development of neovascular complexes in the posterior retina that are richly perfused but nonetheless fail to redress hypoxia in the mid-vitreous. Upregulation of vitreous VEGF may be a consequence of retinal hypoxia at unidentified sites or of chronic inflammatory processes in advanced proliferative diabetic retinopathy.

American Journal of Ophthalmology, 05/07/2011

Blind man sees wife for first time after having a TOOTH implanted into his eye

                                                                  

When Martin Jones met his wife four years ago, he never imagined that one day he would get to see what she looked like. The 42-year-old builder was left blind after an accident at work more than a decade ago. But a remarkable operation - which implants part of his tooth in his eye -  has now pierced his world of darkness. The procedure, performed fewer than 50 times before in Britain, uses the segment of tooth as a holder for a new lens grafted from his skin.

'The doctors took the bandages off and it was like looking through water and then I saw this figure and it was her,' he said today. 'She's wonderful and lovely. It was unbelievable to see her for the first time.' He added: 'When I found out there was a chance I would get my sight back, the first person I wanted to see was her.'

Mr Jones, from Rotherham, South Yorkshire, married his wife Gill, 50, four years ago. By that time he had already spent eight years without his sight after a tub of white hot aluminium exploded in his face at work in a scrapyard. He suffered 37 per cent burns and had to wear a special body stocking for 23 hours a day. He also had his left eye removed.  But surgeons were able to save the right eye, even though he was unable to see through it.

  

During the procedure, a minute section of a patient's tooth is removed, reshaped and chiselled through to grip the man-made lens which is then placed in its core. It is implanted under an eyelid where it becomes covered in tissue. The process requires a living tooth as an implant because doctors suggest there are chances the eye would reject a plastic equivalent.

So a canine - which is the best option due to its shape and size - was taken out of Mr Jones' mouth. A patch of skin is then taken from the inside of the cheek and placed in the eye for two months, where it gradually acquires its own blood supply.  The tooth segment is finally transplanted into the eye socket. The flap of grafted skin is then partially lifted from the eye and placed over its new sturdy base.

Finally, surgeons cut a hole in the grafted cornea to let light through.   

'I have been so fortunate that my sight has been returned . I find it such a simple pleasure being able to see what is going on in the world.'   The eight-hour operation, pioneered by surgeon Christopher Liu, is designed to help patients who have corneal blindness but who are not suitable for traditional corneal transplants.

Quiz

                                                           

A 28-year-old woman presented with a five-day history of redness (see accompanying figure) and mild pain in her left eye. She had not experienced discharge, blurry vision, or photophobia. The patient denied any history of trauma to the eye or participation in an occupation or hobby that put her at risk of a foreign body injury. She did not wear contact lenses. On examination, her uncorrected vision was 20/20 in both eyes.

Question

Based on the patient's history and physical examination, which one of the following is the most likely diagnosis?

  • A. Perilimbal nevus.
  • B. Pingueculitis.
  • C. Pterygium.
  • D. Subconjunctival foreign body.
  • E. Viral conjunctivitis.

Answer: Next Issue

 

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