surface moist and filling in any irregularities in the epithelium. It is avascular and receives its nutrients from the
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1 Melissa Brimer June 25, 2012 Granular Corneal Dystrophy Normal Anatomy/Physiology The cornea is complex and performs several functions. The cornea is transparent and serves as a protective covering for all structures within the eye. The tear film keeps the cornea smooth by keeping its surface moist and filling in any irregularities in the epithelium. It is avascular and receives its nutrients from the conjunctiva, the tear film, and the aqueous humor, and receives oxygen from the air. The cornea is convex in shape and provides about diopters of refractive power. It is fully developed by age two. The cornea is made up of five layers: the epithelium, Bowman s layer, the stroma, Descemet s membrane, and the endothelium. The epithelium is the outermost layer of the cornea and serves as a protective barrier. The epithelium is the only layer that can regenerate. Bowman s membrane can be defined as a layer of condensed stromal tissue that separates the epithelium from the stroma proper. The stroma constitutes 90 percent of the cornea s thickness and is composed of 78 percent water. Descemet s membrane is very elastic and strong, forming the basement membrane of the endothelial cells. The endothelium is responsible for corneal deturgescence and clarity. When endothelial cells die, neighboring cells enlarge and fill the gap of dead cells. Granular Corneal Dystrophy Granular corneal dystrophy is a rare, inherited, autosomal dominant disease caused by a mutation on the BIGH3 gene on chromosome 5q31. The disease is bilateral and often affects both eyes similarly, but it may be asymmetric also. It is characterized by small granules or particles developing in the stromal layer of the cornea. The disease usually presents in the first decade of life, with the granules becoming increasingly larger and more numerous with age. It is a slowly progressive disease that may lead to severe vision loss. Records of almost 8 million enrollees in a national managed care network in the United States, who had an eye- care visit in , were searched for corneal dystrophy claims submitted by an ophthalmologist or optometrist. 27,372 unique individuals received two or more diagnoses of any type of corneal dystrophy, for an overall corneal dystrophy prevalence rate of 897 per million covered lives. Granular corneal dystrophy was the least common, being reported in 167 enrollees (Musch, Niziol, Stein, Kamyar, and Sugar 6 ).
2 Granular corneal dystrophy causes many symptoms that can be disabling. Patients may report decreased or blurry vision, photophobia, pain, foreign body sensation, and tearing. Many symptoms are caused from recurrent erosions. Slit lamp examination may show gray/white sharply demarcated granules that may appear as breadcrumb- like opacities in the stroma. The stromal deposits consist of hyaline, which can be highlighted with Masson trichrome stain on corneal histopathology. Anterior segment photos and corneal topography are useful in showing corneal irregularities. Case Report Granular corneal dystrophy is an inherited disease, and the three patients presented are daughter, mother, and grandmother. Patient A (daughter) is a 21 year- old white female who was diagnosed with the disease at age 4. Vision in OD cc is 20/20 and OS cc is 20/20. Patient A wears OD X 015 and OS X 160. Patient A complains of glare, photophobia, tearing, occasional eye pain, and difficulty driving at night X two years. Patient B (mother) is a 47 year- old white female who was diagnosed at age 5. Vision in OD cc 20/30-2 and OS cc 20/30+2. Manifest refraction with retinoscopy OD X 025 NI and OS X 033 NI. Patient B states blinking makes my vision worse. Patient B complains of sensitivity to light, difficulty driving at night or in bright sunlight, double vision, trouble reading depending on how sore both eyes are, and swollen eyelids. She states she has had sore eyes for about 34 years. Patient B states her eyes stay mildly irritated all the time and get really painful 2-4 times per month with pain of 7-8 in the mornings. Patient B uses Thera tears gel at bed time to relieve pain. She patches both eyes at night when symptoms are extreme to relieve pain from blinking. Patient C (grandmother) is a 70 year- old white lady who was diagnosed at age 6. Patient s vision is OD cc 20/40 and OS cc 20/70. Patient C wears OD X085 and OS x085. Dilated fundus exam was normal with limited view due to granular corneal dystrophy. Patient C had Photo Therapeutic Keratectomy Laser (PTK) done on both eyes 9 years ago with some subjective improvement. She complains of glare from bright sunlight. Patient C states she likes to sit closer to the TV and uses a magnifying glass to see fine print. Patient C has had occasional sore eyes since she was 13 years- old. She states that vision has gradually decreased X 15 years and her vision fluctuates.
3 Patient A Slit lamp photo of OD showing GCD Slit lamp photo of OS showing GCD OD Visante OCT Enhanced Anterior Segment The hyaline deposits are more central OU OS Visante OCT Enhanced Anterior Segment Irregularity is largely central with peripheral sparing OU CIM values are borderline OU Corneal Irregularity Measurement (CIM) is a number or index assigned to represent the irregularity of the corneal surface (Normal CIM are 0.3 to 0.60 microns, borderline 0.61 to 1.0 microns, and abnormal 1.1 to 5.0 microns.)
4 Patient B Slit lamp photo of OD showing GCD Slit lamp photo of OS showing GCD OD Visante OCT Enhanced Anterior Segment The hyaline deposits are more central OU and more numerous on the OS OS Visante OCT Enhanced Anterior Segment
5 Irregularity is mostly central with peripheral sparing CIM values are abnormal in OU Patient C Slit lamp photo of OD showing GCD Slit lamp photo of OS showing GCD OD Visante OCT Enhanced Anterior Segment OS Visante OCT Enhanced Anterior Segment The hyaline deposits are spread throughout the cornea in OU
6 Cornea shows central flattening with steeper periphery as a result of PTK (laser treatment) to remove hyaline opacities OU. The CIM values are extremely abnormal in OU Intervention/Treatment The epithelium contains tiny nerve endings causing the cornea to be extremely sensitive to pain. Erosions are caused by the wearing away of the epithelium overlying the granules growing on the cornea. Erosions cause the eye to have pain, tearing, and light sensitivity. Erosions may be treated with soft bandage contact lens, antibiotics, patching, and antibiotic ointment. The deposits on the cornea become larger over time, gradually decreasing vision. When the patient is having difficulty with daily functions such as driving or reading, surgery may be an option. Excimer laser phototherapeutic keratectomy (PTK) is performed by removing the epithelium manually or with the laser and then applying the laser to the surface of the cornea. The goal is to produce a smoother and clearer cornea. PTK will cause the cornea to become thin, as seen on the topography pictures of Patient C. Lamellar corneal transplantation is performed by removing from one- half to ninety percent of the anterior cornea of the host and replacing it with the same size cornea from the donor. Penetrating keratoplasty (PK) or corneal transplant is full- thickness removal of the cornea of the host which is replaced with a full- thickness graft from the central cornea of the donor. The donor cornea is held in place with interrupted sutures, a continuous running suture, or a combination of the two. Post- treatment management Post- operative care for PTK includes wearing a bandage contact lens and using topical drops such as antibiotics and NSAIDs. Topical steroids may be required after PTK depending on the doctor s preference. The CL is usually worn for 48 hours and the drops used until the epithelium has healed. Clinical follow- up visits occur at 48 hrs, 1, 4, and 12 weeks, and 6 month intervals thereafter for up to 4 years. After a full- thickness corneal transplant, it is important to rest and avoid any strenuous activity. Follow up is usually required the next day with your doctor, and he or she will determine how long the eye patch should remain in place. Graft sutures will usually be left in place for 3 months to a year and may even be left in
7 permanently depending on the suture type. The sutures do not hurt unless they break and become exposed requiring removal. Although the risk of graft rejection is low, steroid drops are required for several months after surgery to prevent rejection and may be required indefinitely. Follow- up appointments are usually one day, one week, one month, and then every 4-6 weeks until month six. At six months, sutures can be removed to modulate the astigmatism they induce. After sutures have been removed, patients may be fitted with hard or soft contact lenses, or spectacles. Follow- ups then occur yearly. It is important to know that vision recovery after PK may take several months. Although cornea transplant may improve vision, the granules may develop in the donor cornea in a 2-3 year period. Even though PK is one of the most successful transplants, graft rejection can still occur. Symptoms of photophobia, decreased vision, irritation, redness, and pain after PK may be signs of cornea rejection. It is important that these symptoms be addressed immediately. Corneal graft rejection in a five year period is less than 35% in the United States. In a study done to evaluate the recurrence rate of corneal dystrophies after PTK, it was found that 3 of 13 eyes with granular corneal dystrophy had clinically significant recurrence with a mean of 40.3 months of follow- up, range 1.1 to 71.2 months (Dinh, Rapuano, Cohen, and Laibson ). Recurrence in the central visual axis is more common following PTK and may require retreatment unless corneal thickness is inadequate. Conclusion Granular corneal dystrophy is a rare, inherited, autosomal dominant disease that clouds the cornea with small granules, which lead to visual problems. When symptoms become severe to the patient, e.g. decreased visual acuity, pain, or photophobia, then PTK, PK, or lamellar corneal transplantation may be performed to restore some vision and to relieve symptoms. At this time there is no cure for this dystrophy, but with identification of the responsible gene (BIG- H3), new genetic and molecular research may someday lead to gene therapy to halt or prevent the disease. Yearly check- ups with your doctor are recommended to monitor the progression of the disease.
8 References 1. Lang, Gerhard K. Ophthalmology: A Pocket Textbook Atlas. 2nd edition. New York: Thieme, ebook. 2. Agarwal, Amar, and Soosan Jacob. Color Atlas of Ophthalmology: The quick- reference manual for diagnosis and treatment. 2nd edition. New York: Thiems, ebook. 3. Stein, Harold A, Raymond M Stein, and Melvin I Freeman. The Ophthalmic Assistant:A Text for Allied and Associated Ophthalmic Personnel. 8th Edtion. Philiadelphia: Elsevier, Print. 4. Dinh, R, CJ Rapuano, EJ Cohen, and PR Laibson. "Recurrence of corneal dystrophy after excimer laser phototherapeutic keratectomy." Ophthalmology. 106(8) (1999): n. page. Web. 20 Jul < Musch, David C, Leslie Niziol, Joshua D Stein, Roheena M Kamyar, and Alan Sugar. "Prevalence of Corneal Dystrophies in the United States: Estimates from Claims Data." Investigative Ophthalmology Ans Visual Science (2011): n. page. Web. 20 Jul < Special thanks to David B. Warner, MD, Assistant Professor of Ophthalmology, Jones Eye Institute, UAMS
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