What is Ophthalmology
Ophthalmology is a branch of medicine that deals with diseases of visual System, including the brain’s visual pathway. An ophthalmologist is a physician who specializes in the comprehensive care of the eyes and visual system and in the prevention of eye disease and injury. The ophthalmologist has completed seven years or more on premedical education, medical school and internship, and three or more years of specialized medical and surgical training in eye care. The ophthalmologist is a physician, who is qualified by lengthy medical education, training and experience; in order to diagnose, treat, and manage all eye and visual system problems. Few ophthalmologists choose to pursue fellowship training in one of the subspecialties in ophthalmology including retina, glaucoma, cornea and refractive surgery, neuro-ophthalomology, and oculoplastics. Ophthalmology is a specialized field, and having a fellowship in one of its subspecialties makes it a highly specialized domain. Dr Falavarjani has completed his fellowship in medical and surgical retina (also known as vitreoretinal fellowship) after having completed full residency training in ophthalmology.
Burden of eye diseases
Eye diseases inflict a heavy burden on the health and well being. Vision loss and blindness are among the top 10 disabilities in the United States, causing substantial social, economic, and psychological effects, including increased morbidity, increased mortality, and decreased quality of life. The economic consequences for the nation are enormous. Vision loss and blindness impose a great social and economic burden on individuals and society. The total annual economic impact of vision problems in the United States reaches approximately $51.4 billion. Good vision is important for good quality of life, and loss of vision leads to disability, morbidity, and loss of productivity. A recent survey, published in the Journal of Archives of Ophthalmology to establish the burden of eye disease in the US population, estimated a total financial burden of major visual disorders of $35.4 billion comprised of $16.2 billion in direct medical costs, $11.1 billion in other direct costs, and $8 billion in productivity losses, in 2004. Annually, the federal government and state Medicaid agencies pay at least $13.7 billion of these costs. According to the CDC (center for disease control and prevention), the total cost of vision problems in the United States was estimated at $145 billion, in 2013.
Posterior segment of the eye
Posterior segment of the eye consists of retina and optic nerve head. The retina is the light-sensitive tissue lining the back of our eye. Light rays are focused onto the retina through our cornea, pupil and lens. The retina converts the light rays into impulses that travel through the optic nerve to our brain, where they are interpreted as the images we see. The retina is a layered structure with several layers of neurons interconnected by synapses. The vitreous is a clear jelly substance that fills inside the eye and attaches to the retina. Posterior segment diseases (known as vitreoretinal diseases) mainly macular degeneration and diabetic retinopathy are the main causes of visual loss among ocular diseases. Overall, posterior segment disorders had a direct medical cost of more than $9 billion in 2013 in United States. Age Related Macular Degeneration (AMD) afflicts approximately 15 million people in the US. Since AMD develops with age, with a growing aging population the trajectory is daunting. According to the National Eye Institute, 2.1 million Americans had advanced (blinding) form of AMD in 2013 which is estimated to increase to 3.7 million by 2030. Similarly, Diabetic retinopathy is a major cause of blindness in the United States, causing 12,000–24,000 new cases each year. In 2010, 7.7 million Americans had diabetic retinopathy, the number is estimated to be 11.3 million by 2030 and 14.6 million in 2050.
Summary of researches published by Dr Ghasemi Falavarjani
A. Diabetic retinopathy:
Diabetic retinopathy is the most important ocular complication of diabetes mellitus. In this disease, the retina is affected by the changes in the capillaries leading to the hemorrhage, accumulation of fluid in the macula (macular edema), retinal detachment and finally blindness. According to the National Eye Institute, diabetic retinopathy is a leading cause of blindness in American adults. From 2010 to 2050, the number of Americans with diabetic retinopathy is expected to nearly double, from 7.7 million to 14.6 million. This shows the importance of research on diabetic eye disease.
• Retinal detachment due to the diabetic retinopathy needs surgery. The surgery in these eyes is very difficult and the outcomes are poor in nearly 30% of cases. In a research projects, Dr Falavarjani showed that the intravitreal injection of bevacizumab immediately before surgery, significantly facilitates the surgery and improves the outcomes. Bevacizumab, is a drug that is injected inside the eye to stabilize the blood vessels and treat edema. This article is among the first published studies in recent years that changed the practice of surgeons to use this benefit for their patients. In addition, in another research, he showed for the first time, that the injection of bevacizumab into the silicone oil inside the eye has therapeutic effects on neovascular glaucoma.
• Neovascular glaucoma is one of the difficult-to-treat complications of the surgery in diabetic eyes. This study was published in the journal of Eye (a prestigious journal of Nature journal collection).
• In another original research, Dr Falavarjani evaluated the role of intraocular injection of methotrexate after surgery for diabetic retinopathy. This is very important because the surgery fails in 30% of patients and many researchers believed that inflammation has a critical role in failure. He used methotrexate which is a potent anti-inflammatory drug and showed that its use is not effective in preventing complications. This research was published in the journal of Eye in 2015 and led to research for the mechanisms other than inflammation for the failure of the surgery.
• Macula which is the most important part of the retina is affected in 25% of diabetic patients. Intravitreal injections are the standard of care in eyes with diabetic macular edema. However, approximately 30-40% of eyes do not respond to the injections properly. The alternatives in these eyes are limited, very expensive and with poor results. In an original research, he evaluated the effect of intravitreal injection of methotrexate which is a cheap and available drug in these eyes. The result was published recently in the journal of Graefes Archives of Clinical and Experimental Ophthalmology (May 2016) and showed that methotrexate in effective in cases with diabetic macular edema which are resistant to standard treatments.
• In addition, in routine practice, multiple injections are needed for the treatment of macular edema and each injection carries the risk of complications such as infection, hemorrhage and retinal detachment. To find an alternative route of injection, he conducted a research to see if the periocular injection (instead of injection into the eye) is effective.
B. Retinal surgery developments and original researches
Dr Falavarjani conducted several research studies on the surgical treatment of various retinal diseases. He has two surgical methods, specific to practice that was then popularized after publication. In one surgical technique, he presented the results of our surgical technique for re-fixation of intraocular lens. Insertion of intraocular lens is a uniform requirement in every cataract surgery. In some eyes, insertion of intraocular lens is very difficult because of intra-operative complications and needs specific vitreoretinal surgical approaches. He described this technique to attach the intraocular lens to the ocular wall with a new approach. In another technique, he reported a new surgical approach for removal of heavy silicone with fewer complications than routine approach.
• Silicone oil is necessary to be injected inside the eye at the end of surgery for retinal detachment to keep the retina in place for a temporary period of time and then is removed. The routine approach needs specially designed pumps and vitrectomy machine and may be associated with significant complications. His approach does not need a suction pump or specific machine and the rate of complications was low. This reduces the instrument costs from approximately $400-500 to approximately $50-100. The technique was published in journal of Retina, a peer-reviewed, highly prestigious journal in ophthalmology, in 2011. The video of this surgery using this technique was the winner of the “best video” of the Annual Meeting of Iranian Society of Ophthalmology.
• In one original article, he reported the results of our study with a surgical technique, scleral buckling, for these eyes with a more favorable outcome. The study was published in the Journal of Eye in 2015. Retinal detachment is a common retinal disease (about 1 in 10,000 persons per year) that needs immediate surgical intervention to save the vision. Those eyes with retinal detachment and subretinal proliferation are very difficult to manage and the treatment of choice is controversial. Generally, the surgeons prefer to do mechanical vitrectomy which is associated with significant complications (in approximately 40%).
• The rate of complication in retinal detachment surgery is high and about 10-30% need re-operation especially if the proliferative retinopathy is present. Therefore, many researchers are working on different ways to reduce the complications. Unfortunately, the results are not promising and the research in this field is ongoing. Based on the current understanding of the causes of complications, several researchers proposed that the use of bevacizumab, a drug that stabilizes the vessel walls may reduce the complications. In one original research, he showed that in contrast to common belief, adjuvant intraocular injection of bevacizumab at the end of surgery has no benefit on surgical outcomes. The study was presented in the European Society of the Retina Specialists (Euretina), Hamburg, 2013 and published in the Journal of Eye in 2014.
• Surgery in eyes with ocular trauma is always challenging, especially for those with intraocular foreign body. The eye is lost in many eyes despite appropriate treatment. In an original article in Middle East African Journal of Ophthalmology (2013), he reported his experience with surgery in these eyes. The outcome was excellent in saving eyes. The results were also presented in the World Ophthalmology Congress, Abu Dhabi, 2012.
• Dropped nucleus is a common complication of cataract surgery (about 3%). This complication needs a vitreoretinal surgery in order to remove the nucleus. Traditionally, the removal of nucleus body needs a special instrument, fragmatome, that is not available in most operating rooms. In his method that was presented in the World Ophthalmology Congress, Abu Dhabi, 2012 and published in the Journal of Ophthalmic and Vision Research (2012), he reported a simple approach using a widely available instrument (phacoemulsification prob) with promising results.
C. Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION):
NAION is the ischemic injury of the optic nerve head that affects between 2.3 and 10.3 people per 100,000 individuals per year making it one of the most common cause of acute visual loss in patients over the age of 50. There are approximately 6000 new cases per year. Unfortunately, the exact cause of this disease is unknown and also, the disease has no proven treatment.
• First, he conducted several research studies to understand the risk factors and associations of this disease. In one original research, the clinical profile and risk factors of patients with NAION during 5 years, was published in the Journal of Archives of Iranian Medicine in 2009. He found that the NAION is more prevalent in diabetics and hypertensive patients. Then, he showed that ocular dimensions are not associated with this disease in contrast of some previous reports. Then, he published the results of his original research on association of the carotid wall thickness changes with this disease in the British Journal of Ophthalmology. Then, he evaluated the characteristics of the optic nerve head in relation to the adjacent structures. The finding was very interesting and showed that the traction of the vitreous jelly inside the eye is more prevalent in eyes with NAION (Published in Iranian Journal of Ophthalmic Research, 2006).
• In the most important study, and according to his previous research, Dr Falavarjani and his professors in the Iran University of Medical Sciences hypothesized that the traction by the vitreous jelly inside the eye can cause NAION. In this original research, the traction was removed by an advanced vitreoretinal surgery and they showed that this approach is effective in eyes with confirmed traction.
• Erythropoietin is a commonly used drug in anemic patients. Recently, the protective effects of erythropoietin on neurons have been shown in several animal models. Considering that the NAION is a disease of optic nerve and for the first time in the literature, they conducted an original research to evaluate the effect of injection of Erythropoietin inside the eye in NAION. The drug was effective in about 60% of eyes which is apparently higher than the natural course. The study was published in British Journal of Ophthalmology in 2011.
D. Retinal imaging
This is a field of continuous development. Retinal imaging is a requirement for diagnosing of retinal diseases. Without a suitable retinal imaging, the diagnosis is misleading. For this reason, every retinal clinic should have several imaging instruments including OCT, fluorescein angiography and electrophysiology testing instruments. The effect of each drug on retinal disease is measured by the visual acuity. But visual acuity is a subjective measure and is not reliable. For this reason, the effect of drug should be confirmed by specific imaging modalities. Currently, retinal imaging confirmation is a requirement for new drug approval by FDA.
• Optical Coherence Tomography (OCT) uses the reflection of laser light from retinal layers to create images from retina and measures the thickness of the retinal layers. The instrument is very precise with a resolution of up to 5 micrometers. In 3 original researches, Dr Falavarjani has focused on errors associated with OCT measurements. In one research, he showed that frequency of a specific type of error in OCT measurements in a routine daily practice is high. After this study, he conducted another research to evaluate the effect of this error on thickness measurements and showed that this error changes the measurements significantly and the change is more in diabetic eyes. This study was published in European Journal of Ophthalmology in 2015. In the third research, he evaluated the changes in the OCT thickness before and after meal. He showed that in diabetics, the retinal thickness may be affected by the fasting status (and not due to the effect of a drug), so, the measurements should be performed at the same time relative to the fasting status. This original article was published in Journal of Current Ophthalmology in 2015. In these researches, he showed that measurement of the retinal thickness may be affected by factors other than the effect of drug.
• Diabetic eyes usually need macular laser photocoagulation for the treatment of retinal edema. Laser therapy, however, may change the results of some imaging modalities. In an original research, he showed that retinal nerve fiber layer thickness measurements around the optic nerve head is not affected by laser treatment and is reliable for future measurements.
• Retina is considered a part of brain. Retinal nerve fibers constitute a layer of the retina and continue to the brain. In an original research, he helped the neurologists to show that in the Parkinson´s disease (that originally affects brain), the retinal nerve fiber layer thickness measured by OCT is affected. This shows that OCT can be used to predict the disease type in some brain diseases.
• Fluorescein angiography is a type of retinal imaging that shows accumulation of the fluid from leaking abnormal vessels. In an original study, he created a semiautomatic approach for measurement of lesions in the fluorescein angiography images using advanced analysis software that is more predictable than previous approaches. Since fluorescein angiography is a commonly used tool for a wide variety of ocular diseases including diabetic retinopathy and age related macular degeneration, this method is of potential interest.
E. Endophthalmitis
Endophthalmitis or intraocular infection is a nightmare for an ophthalmic surgeon. It is an urgent situation, difficult to treat and often with poor outcome. This infection usually leads to legal blindness in the affected patients. His research on this disease focused on the etiologies, risk factors and treatment outcomes.
• Obstruction of the nasolacrimal duct is one of the most important etiologies of endophthalmitis. Therefore, the surgery for relief of obstruction should be done before any intraocular surgery. In one original research, he and his colleagues showed that intraocular surgery (like cataract surgery) is safe after 7 weeks after opening nasolacrimal obstruction. This study was published in the Journal of Ophthalmic Plastic and Reconstructive surgery in 2014.
• In one original article published in Middle East African Journal of Ophthalmology in 2012, he presented the clinical characteristics and antibiotic sensitivity and treatment outcome of different types of endophthalmitis. This is the largest report from Iran. In the second original research published in the Journal of Ocular Immunology and Inflammation in 2016, he showed that the outcome of a special type of endophthalmitis caused by Pseudomonas species is poor despite proper treatment.
• In two separate original studies, Dr Falavarjani determined the prevalence of endophthalmitis after intravitreal injections and showed that the prevalence is not related to the use of prophylactic antibiotics. Prescription of antibiotics for prophylaxis of endophthalmitis was an area of strong controversy. In the first study that was published in the Journal of Retina in 2013, he showed that antibiotic eye drops are not beneficial for preventing endophthalmitis. The second study, confirmed the results of first study in a different setting (published in Canadian Journal of Ophthalmology in 2015). These researches have strong impact on elimination of the use of antibiotics in intravitreal injection and some national guidelines (e.g. Spanish expert guidelines for intravitreal injections in macular degenerations) referred to my article as the strong evidence.
F. Age-related macular degeneration (AMD)
Age related macular degeneration is one of the most common retinal diseases among elderly and the treatment of choice for wet type of the disease is intraocular injections. Without treatment, the disease leads to legal blindness in most of eyes.
• Several drugs are available for injections. In 2009, when Dr Falavarjani and his colleugues published their results on the treatment of AMD, the widely used drug was ranibizumab that is very expensive (approximately $2000 for each injection. They conducted their research using a less expensive drug, bevacizumab ($50 for each injection), and showed that drug is effective and also two doses of this drug (1.25 and 2.5 mg) has similar efficacy. Currently, bevacizumab is the most widely used drug in AMD.
• In two studies, they collaborated in conducting the research to determine the genetic variants of AMD in Iranian population. The results were published in two articles in Journal of Ophthalmic and Vision Research (2014) and Report of Biochemical and Molecular Biology (2015). These are the first reports from the Iranian population, and the findings are of importance for future genetic therapy.
G. New imaging modalities
The imaging of the posterior segment is rapidly developing and several major companies are focusing to develop advanced retinal imaging instruments and spending millions of dollars to reach this goal. Traditionally, to see the vessels of the retina and optic nerve head, the fluorescein dye was necessary to be injected into the veins. OCTA is a new technology (introduced in 2014) that visualize the vessels inside the eye without the need for injection of the dye. This non-invasive imaging system is rapidly developing to be incorporated as a main modality in clinical trials and clinical practice. Until recently, the imaging of the peripheral part of the retina was not possible. This is very important because peripheral part of the retina is the site of several diseases including diabetic eye disease and vascular occlusions. Ultra-wide-field imaging allows easy assessment of the peripheral retina and is being processed to be a standard of care in the retinal practice. Image analysis needs an ophthalmic specialist to be familiar with the disease, the imaging system and the advanced methods for the analysis of the images. Dr Falavarjani used advanced image analysis software for special analyses of the images.
• In a research project, he evaluated the utility of the OCTA in optic nerve diseases. This is the first original research in ophthalmic literature describing the vascular networks around the disc in eyes with different types of optic neuropathy. In this research, they showed that vascular change is easily detectable in different optic nerve diseases that traditionally needed invasive and expensive procedures to be diagnosed. The article has been published in the Journal of Retina.
• In the second project, he evaluated the frequency and types of the errors in the OCTA images. OCTA imaging is a new modality and its errors remain to be completely determined. He defined different types of OCTA error and showed that the errors may be easily misleading. Each retinal clinician and scientist should be familiar with these OCTA errors. In other research, he helped his colleagues in UCLA to show that image quality affects the interpretations of the images.
• In another research project, he focused on the multimodal imaging. Multimodal imaging means using different imaging instruments (OCT, OCTA, ultra wide field imaging) to explore the approach to the disease. This is the first original research in the ophthalmic literature showing a correlation of the Ultra-wide-field imaging with OCTA using advanced image analysis.
• The use of anti-VEGF drugs are the standard treatment for macular edema in diabetic eyes and vascular occlusions. However, there is a longstanding debate on the effect of these drugs on small capillaries in the fovea. In another research, using OCTA, he showed that anti-VEGF agents are safe for the macula in eyes with macular edema.