Who is PIE Person? The hero of the posterior segment, of course. Just as PIE Person’s worst enemy is Evil Eye, each ocular-disease-fighting ophthalmologist has their own nemesis to vanquish. So what conditions are considered the most villainous – and what weapons can conquer them? We asked three sight-saving superheroes those questions … and their responses might surprise you.
Superhero: Dr. Au Eong Kah Guan (a.k.a. The Retina Rescuer), medical director and senior consultant, Singapore International Eye Cataract Retina Centre at Mount Elizabeth Medical Centre and International Eye Cataract Retina Centre at Farrer Park Medical Centre, Singapore
Villain: Central Retinal Artery Occlusion (CRAO)
“Central retinal artery occlusion (CRAO) is the worst condition affecting the posterior segment; in addition to often blinding a person, it’s associated with an increased risk of stroke, acute myocardial infarction and death,” said Dr. Au Eong. The life expectancy of patients with CRAO is 5.5 years compared to 15.4 years for an age-matched population without the disease. “In most cases, profound loss of vision occurs despite treatment.”
“CRAO is an acute, painless condition that is typically caused by thrombosis or embolism leading to ischemia of the retina and optic nerve head, resulting in severe vision loss,” he explained. This condition damages cells rapidly and retina survival depends on the degree of collateralization and the duration of retinal ischemia. Prompt diagnosis and early treatment to dislodge or lyse the offending embolus or thrombus is crucial to avoid irreversible retinal damage and blindness.1
Thankfully, Dr. Au Eong doesn’t see this condition frequently – about once or twice a year. This corresponds with the low reported incidence rate: CRAO affects approximately 1 per 100,000 people with less than 2% presenting with bilateral involvement. The mean age for symptoms is 60, and risk factors are similar to other thromboembolic diseases, including: hypertension, smoking, hyperlipidemia, diabetes, hypercoagulable states, and male gender. Approximately one-third of patients with CRAO have clinically significant ipsilateral carotid artery stenosis.1 Another study found that previously undiagnosed vascular risk factors were found in 78% of all CRAO patients.2
Weaponry: Still seeking a super-solution
Unfortunately, there is no consensus for optimal treatment of CRAO. Current standard treatment options are aimed at restoring retinal perfusion/oxygenation and include: immediate digital ocular massage to induce oscillations of intraocular pressure and dislodge the offending thrombus; intraocular pressure reduction with acetazolamide, mannitol, topical timolol (anti-glaucoma eyedrops), or anterior chamber paracentesis (often recommended in conjunction with digital ocular massage); breathing into a paper bag or inhaled 10% carbon dioxide to induce respiratory acidosis and vasodilation; and/or supplemental oxygen.1 To this list, Dr. Au Eong added hemodilution, corticosteroids, systemic pentoxifylline and sublingual isosorbide dinitrate as possible therapy options. He notes that, unfortunately, none of these treatments have shown to be more effective than placeboes. (This looks like a job for PIE Person!)
Another therapy option using local intra-arterial fibrinolysis (LIF) to treat CRAO showed some initial promise. “However, the first randomized clinical trial [by the European Assessment Group for Lysis in the Eye (EAGLE)] did not demonstrate an improved visual outcome with treatment,” said Dr. Au Eong. According to the study, patients treated within 12 hours were more likely to profit from treatment. But in a multivariate analysis, there was no clear trend to benefit from LIF – even in patients treated early. Based on this preliminary report (on a rather small sample size), the authors did not recommend LIF in CRAO patients.3
A meta-analysis by Schrag et al. (2015) found that some of the more conservative therapies like ocular massage, anterior chamber paracentesis, and hemodilution actually worsened visual outcomes – calling them futile, and possibly harmful. They did find, however, that systematic fibrinolysis was beneficial within 4.5 hours of symptom onset and suggest that a clinical trial of early systemic fibrinolytic therapy for CRAO is needed.4
Dr. Au Eong agrees that systemic fibrinolysis within 4.5 hours of CRAO has not yet been evaluated in a randomized controlled clinical trial and is therefore, warranted.
“Systemic fibrinolytic therapies are simpler and faster to deploy than LIF for CRAO,” he added. “Rapid administration of systemic fibrinolytic agents has been proven to be a feasible and effective treatment for acute ischemic stroke, but only within 4.5 hours of symptom onset. For this reason, systemic fibrinolysis may improve the efficacy of treatment for CRAO.”
Superhero: Dr. Low Cze Hong (a.k.a. Macula Man), senior consultant ophthalmologist and medical director, C H Low Specialist Eye Centre, Mount Elizabeth Medical Centre and Hospital, Singapore
Villain: Age-related macular degeneration (AMD)
The good news is people are living longer. The bad news? As life expectancy increases, so does the probability of acquiring an age-related disease – like age-related macular degeneration. According to Dr. Low, “AMD is a dreaded disease – and it though used to be a rare disorder in Singapore, it is now fairly common.”
AMD is a leading cause of irreversible blindness of adults over 50 years old, with a global prevalence of 170 million. It is the leading cause of visual disability in the industrialized world and the third leading cause globally.5 As aging is the greatest risk factor, the prevalence of AMD will continue to rise as the population ages.
“Initially, visual functions are greatly impacted with deterioration of central visual acuity, color and reading vision,” explained Dr. Low. “As time goes on – in some cases, even with adequate treatment – further visual deterioration will result in near total loss of vision.” In its most advanced stages, AMD deprives an individual of his or her ability to perform basic activities such as reading, recognizing faces, and driving.
According to the American Academy of Ophthalmology (AAO), although an estimated 80% of AMD patients have non-neovascular or atrophic (dry) AMD, the neovascular form (wet) is responsible for nearly 90% of the severe central visual acuity loss associated with AMD.6
Weaponry: The tried and true “Needle in the Eye”
Like CRAO, there is no definitive cure for AMD. And even though there are therapy options that can halt the progression of the disease, the condition can still worsen – even with treatment. Generally, the first line of recommended therapy for neovascular AMD is anti-vascular endothelial growth factor (anti-VEGF). Injected intravitreally, anti-VEGF aims to block the growth of abnormal blood vessels in the eye to prevent vision loss.
“We are fortunate to have many new anti-VEGF agents at our disposal,” said Dr. Low. “These various regimens of treatment have by-and-large halted the disease’s progression in patients who have early detection and intervention, persist in follow-up and repeated treatment, and can afford it – either through public or self-funded health schemes.”
The anti-VEGF delivery system is simple – through a needle via the pars plana. Dr. Low adds that meticulous hygiene and asepsis is vital. In addition, the therapy is generally well tolerated and rarely associated with serious adverse events like infectious endophthalmitis or retinal detachment.6
Superhero: Dr. Ashish Sharma M.S. (a.k.a. The DME Destroyer), innovator andhead, MII RetCam Development Team and consultant retina and head research, Lotus Eye Hospital and Institute, Coimbatore, TN, India.
Villain: Diabetic Macular Edema (DME)
According to Dr. Sharma, the biggest sight-threatening villain he encounters is diabetic macular edema (DME). “There is a high prevalence in the young working population [in India] – we see these cases every day,” he shared.
This is because diabetes is approaching a potential epidemic in India, with more than 62 million individuals currently diagnosed with the disease. It’s predicted that by 2030, up to 79.4 million individuals in India may have diabetes. To make matters worse, Indians are more susceptible to diabetic complications like DME at an early age (20 to 40 years), compared to Caucasians (> 50 years).7 DME is responsible for most of the visual loss experienced by patients with type 2 diabetes,8 making this a major public health concern.
“My patients fear that they will lose their livelihood,” said Dr. Sharma. “Furthermore, the injection burden [with anti-VEGF] is sometimes too high.”
Weaponry: Needles and implants supercede lasers
Traditionally, focal or grid laser photocoagulation has been a treatment for DME. However, recent studies on the effect of anti-VEGF substances in DME, showed resolution of the edema and visual acuity gain. Thus, anti-VEGF therapy has become a prominent treatment for DME. A recent meta-analysis found that anti-VEGF drugs are effective at improving vision in people with DME, with 3 to 4 in every 10 people likely to experience an improvement of 3 or more lines visual acuity at one year.9 Intravitreal steroids, also play a role in the management of DME, particularly in refractory cases, due to their anti-inflammatory effect.10
Dr. Sharma agrees and recommends anti-VEGF as primary therapy for phakic DME patients. For pseudophakic DME patients, he prefers the dexamethasone intravitreal implant Ozurdex (Allergan, Inc., Irvine, CA). Dexamethasone implants like Ozurdex, tend to be reserved for patients unresponsive to anti-VEGF therapy and may be considered first line of treatment for pseudophakic patients, or those with impending cataract surgery.11
“If injections are regular, I have good success, with 70 to 80 percent of patients reporting improvement,” said Dr. Sharma. He says that while it is a safe and effective treatment, for best results long-term continuous therapy is required.
Each of these villains (CRAO, AMD and DME) remain a threat to sight for millions worldwide. Clearly, there is more work to be done – but every day, with new innovations for diagnosing and treating disease in the posterior segment, PIE Person (and his team of Eye Avengers) get closer to vanquishing Evil Eye … for good.
Eye Avengers Assemble!
Even superheroes need to recharge their batteries. For eye-sight avengers, this “recharging” often takes place at ophthalmology congresses worldwide – where heroes from far-flung countries and the most specific sub-specialty surgeons converge to increase their superpowers (in this case, knowledge). In 2018, these are the conferences where the PIE People staff of PIE Magazine will likely be found:
- Asia-Pacific Academy of Ophthalmology (APAO), Hong Kong, Feb. 8 to 11, (Booth #3A-04)
- All India Ophthalmology Congress (AIOC) 2018, Coimbatore, India, Feb. 22 to 25
- Advanced Vitreo Retinal Techniques and Technology (AVRTT@6), Ahmedabad, India, March 17-18
- Asia-Pacific Glaucoma Congress (APGC) 2018, Busan, South Korea, Apr. 13 to 15
- The Association for Research and Vision and Ophthalmology (ARVO), Honululu, Hawaii, Apr. 29 to May 3
- World Ophthalmology Congress (WOC), Barcelona, Spain, June 16 to 20
- Asia-Pacific Association of Cataract and Refractive Surgeons (APACRS), Chiang Mai, Thailand, July 19 to 21
- 8th EURETINA Congress, Vienna, Austria, September 20-23
- European Society of Cataract and Refractive Surgeons (ESCRS), Vienna, Austria, Sept. 22 to 26
- American Academy of Ophthalmology (AAO), Chicago, Illinois, USA, Oct. 27 to 30
- The Royal Australian and New Zealand College of Ophthalmologists (RANZCO), Adelaide, Australia, Nov. 17 to 21
- Asia-Pacific Vitreo-retina Society (APVRS), Seoul, South Korea, Dec. 14 to 16
Editor’s Note: PIE Person defined: PIE stands for Posterior Segment – Innovation – Enlightenment, as in PIE Magazine. The 33rd Asia-Pacific Academy of Ophthalmology Congress (APAO 2018) was held in Hong Kong on February 8-11, 2018. Media MICE Pte Ltd, PIE Magazine’s parent company, was the official media partner of APAO 2018.
1 Farris W, Waymack JR. Central Retinal Artery Occlusion. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2017. Available at: https://www.ncbi.nlm.nih.gov/books/NBK470354/. Accessed on 18 January 2018.
2 Callizo J, Feltgen N, Pantenburg S, et al; European Assessment Group for Lysis in the Eye. Cardiovascular Risk Factors in Central Retinal Artery Occlusion: Results of a Prospective and Standardized Medical Examination. Ophthalmology. 2015;122(9):1881-1888.
3 Pielen A, Pantenburg S, Schmoor C, et al; EAGLE Study Group. Predictors of prognosis and treatment outcome in central retinal artery occlusion: local intra-arterial fibrinolysis vs. conservative treatment. Neuroradiology. 2015;57(10):1055-1062.
4 Schrag M, Youn T, Schindler J, et al. Intravenous Fibrinolytic Therapy in Central Retinal Artery Occlusion: A Patient-Level Meta-analysis. JAMA Neurol. 2015;72(10):1148-1154.
5 Pennington K, DeAngelis M. Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors. Eye Vis (Lond). 2016;3:34.
6 AAO Retina/Vitreous PPP Panel, Hoskins Center for Quality Eye Care. Age-Related Macular Degeneration PPP. Jan 2015. Available at: https://www.aao.org/preferred-practice-pattern/age-related-macular-degeneration-ppp-2015. Accessed on 18 January 2018.
7 Kaveeshwar SA, Cornwall J. The current state of diabetes mellitus in India. Australas Med J. 2014; 7(1):45-48.
8 Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis (Lond). 2015;2:17.
9 Virgili G, Parravano M, Evans JR, et al. Anti-vascular endothelial growth factor for diabetic macular oedema: a network meta-analysis. Cochrane Database Syst Rev. 2017;6:CD007419.
10 Berco E, Rappoport D, Pollack A. Treatment options for diabetic macular edema. Harefuah. 2017;156(2):109-113.11 Mehta H, Gillies M, Fraser-Bell S. Perspective on the role of Ozurdex (dexamethasone intravitreal implant) in the management of diabetic macular oedema. Ther Adv Chronic Dis. 2015;6(5):234-245.