Ocular Manifestations of Diabetes Mellitus - Coursework Example

Ocular manifestations of diabetes mellitus Introduction The ocular manifestations of diabetes mellitus (DM) are numerous and include retinopathy, cataract, glaucoma, and neurophthalmic disorders. These associated conditions increase with age and duration of disease whether type-1 or type-2. The current emphasis in the management of these diseases is on the development of cohesive multidisciplinary screening and education programs, and to a better understanding of the cellular and molecular mechanisms that underlie the disease. The role of associated and potentially modifiable systemic factors is also now recognized and it is hoped that early intervention with systemic and local therapies help manage the diabetic eye disease better1. The majority of general practitioners and physicians are acquainted with the clinical risk factors, presentation and management of diabetic retinopathy. However, only a handful of doctors are sufficiently aware about further ocular signs that occur more commonly in their diabetic patients. Our evidence based review, aims to expose these important clinical findings. We aspire that doctors become more involved in screening for a wider range eye diseases in their patients with diabetes; recognize when patients should be referred to the ophthalmologist; and understand and support follow-up for these patients. Surveillance and treatment of diabetes-related manifestations should be a critical part of routine management of all patients with diabetes. With appropriate training and regular practice, sensitivity for the screening examination is achievable with good specificity, combined with regular screening; this will attain an appropriate level of detection. Sources and selection criteria We reviewed studies on ocular signs of diabetes patients from Medline. We specifically excluded “diabetic retinopathy”. For each ocular condition, please describe in the following sequence: 1. how common is this condition in patients with diabetes compared to normal subjects; 2. clinical presentation of the condition; 3. Why does this occur more frequently in patients with diabetes; 4. current recommended therapies and prevention measures. –JJW ## Orbital Infection Small case series have shown that patients with diabetes are susceptible to fungal orbital infection such as orbital cellulitis2. In 60-80% of cases of rhino-orbital-cerebral mucormycosis (ROCM), diabetes was a predisposing factor3 ## Can you please provide data on the likelihood of this infection in patients with diabetes compared to normal subjects who do not have diabetes? Otherwise, what data support the claim that patients with diabetes are susceptible to this infection? Why are they susceptible?– Orbital cellulitis presents as lid edema and redness, distention, proptosis, and significant pain upon palpation. Additionally, there will be diplopia from extraocular motility limitations. It can be differentiated from preseptal cellulitis with the following signs: painful restricted eye movements, proptosis and globe displacement. In severe cases, compression of the optic nerve can cause colour vision defects, visual loss and afferent pupillary defect. Orbital infections may develop via direct inoculation, extension from adjacent structures or hematogenous spread. Mucormycosis is an important consideration in a diabetic patient presenting with sudden loss of vision, eyelid gangrene or endophthalmitis and is potentially fatal4. Diabetic patients with mucormycosis frequently present with rhino-orbital cerebral involvement{reference?}. Prognosis depends on the organism and extent of inflammation. Those who have altered sensorium, facial necrosis, palatal perforation and cerebral involvement at presentation have poor outcome. Combined approach with amphotericin B and appropriate surgery is an effective method of approach to the treatment of this possible fatal disease5. The patient may develop blindness from orbital apex syndrome, cavernous sinus thrombosis, meningitis or orbital / periorbital / cerebral abscess. Rarely, Aspergillosis may also cause orbital cellulitis6. Orbital cellulitis must be treated with inpatient admission, intravenous antibiotics +/- surgical drainage. Dry eyes The association between diabetes and dry eyes has been examined in numerous experimental and clinical studies7. ##Is there an association? How strong is the association? –JJW## The signs of conjunctival and corneal dryness can be extremely variable, ranging from foreign body sensation to hypersecretion. In a study by Namara and others8, thay reported that hyperglycemia affected corneal hydration control. They also suggested that there was reduced corneal recovery from hypoxia in those with diabetes than did control subjects. In those with insulin dependent diabetes, reflex tearing is significantly decreased. In contrast, unstimulated basal tear flow and tear film break up time are normal. The longer interblinking time, results in decreased blinking rate. The tear protein patterns of diabetic patients are very different in the number and intensity of spots from those of healthy subjects. Because of these changes, the quality of tears is affected and the quantity is decreased9. This change in the pattern of tear proteins probably is another reason for dry eyes. These alterations in the diabetic tears are correlated with the duration of the diabetic disease10. ##Why does this occur in patients with diabetes and why is it associated with diabetic duration? –JJW These tear changes along with squamous metaplasia, and goblet cell loss, all of which seem to evolve in close proximity to the status of metabolic control and peripheral neuropathy lead to dry eyes and consequent changes in the conjunctiva. ## The mainstay of therapy is artificial tears and lubrication. However, severe cases may be difficult to control and may cause corneal ulceration, with possible perforation. Corneal abrasions Fewer studies have examined the epidemiology of corneal abrasions in patients with diabetes. These patients often have reduced corneal sensitivity ## in proportion to? ## Do you mean that proportions of patients with reduced corneal sensitivity increase with increasing duration of the disease and severity of neuropathy?11, ##Cornea becomes thicker in a relatively early stage of diabetes. One possible pathway is increased formation and accumulation of advanced glycation end-products (AGEs) in the cornea12.## Why?## but does not further change with the degree of neuropathy. A reduction in neurotrophic stimuli in severe neuropathy may induce thinning of corneal epithelium that may lead to recurrent erosions. In addition, patients may present with photophobia, blurred vision and hyperaemia. Corneal abrasion, recurrent corneal erosion, striate keratopathy and corneal oedema are more likely because of poorer adhesion between the basement membrane of the corneal epithelium and the corneal stroma. ## Why does this occur in patients with diabetes? –JJW## The aldose reductase pathway probably plays an important function in epithelium regulation because aldose reductase inhibitors are known to expedite the healing of corneal abrasions. Erythrocyte aldose reductase increase has been noted in type 2 patients, leading to high accumulation of sorbitol which can damage the corneal epithelium13. Treatment includes topical antibiotics, topical cycloplegic (short term), and patching for 24 hours if indicated (size>2cm, non-organic material, non-contact lens wearers). Patients should never be prescribed a topical anaesthetic since these agents are toxic to the cornea and can result in non-healing epithelial defects. Confocal microscopy allows early detection of beginning neuropathy, because decreases in nerve fibre bundle counts precede impairment of corneal sensitivity14. Glaucoma Approximately 5% of the population with DM develop glaucoma, compared with about 2% of the general population15. 1) Primary open angle glaucoma (POAG) A number of population-based studies have found a positive association between diabetes and open angle glaucoma or between diabetes and raised intraocular pressure, the major risk factor for glaucomatous optic nerve damage (Table 2).Among persons without a diagnosis of diabetes, 18% of patients with POAG have an abnormal glucose tolerance test. Patients with diabetes are more vulnerable to visual field loss associated with intraocular pressure16 ## any data on this? –JJW ##. Microvascular damage from diabetes could impair blood flow to the optic nerve, resulting in ischaemic optic nerve damage. Diabetes could also interfere with the auto-regulation of the posterior ciliary circulation, which may exacerbate glaucomatous neuropathy. Those with diabetes #Please change the wording here## often have concomitant cardiovascular risk factors (e.g., hypertension) which may also affect vascular perfusion of the optic nerve head17. It has also been suggested that although diabetics## with POAG have background retinopathy, they? do not appear to progress to proliferative retinopathy ##any evidence on this?##, presumably due to their glaucomatous state or genetic make-up {Reference?}. Treatment includes topical eye drops (prostaglandin analogue, β-blocker, α2-agonist, carbonic anhydrase inhibitor), argon / selective laser trabeculoplasty, trabeculectomy or shunt procedures. 2) Neovascular glaucoma (NVG) Epidemiological studies have shown a consistent association between neovascular glaucoma and diabetes18. Neovascularization of the iris usually is seen commonly in insulin dependent, long standing or poorly controlled diabetics. There are usually no symptoms until the pressure builds and the patient presents with decreased vision, severe pain, redness and watering. Ocular tissue hypoxia often causes production of angiogenic factors that stimulate the formation of neovascular vessels of the iris and anterior chamber angle, that may eventually contract and cause angle closure. With the formation of synaechiae, angle closure becomes permanent and results in high elevated intraocular pressure. Medical management (topical steroids, cycloplegics (atropine) and IOP lowering agents) is rarely adequate. To salvage the eye, neovascular glaucoma requires aggressive surgical intervention such as trabeculectomy, tube-shunt procedures or cyclodestruction (eg cyclodiode) depending on visual prognosis19. Cataracts Abundance of data from clinical, epidemiological and basic science studies reveal that diabetics are at higher risk for acquiring cataracts. (Refer to table 1). Persons with both type 1 and 2 diabetes are at higher risk for the development of cataracts. Cataracts are 2-4 times more prevalent in patients with DM than in the general and they occur at younger ages and progress more rapidly20. The risk of cataract (most strongly with rapid onset snowflake cataract, posterior subcapsular cataract and to a lesser extent, cortical cataract, but not nuclear cataract21) increases with length of disease and poor glycaemic control22. Cataractogenesis has been postulated to be due to or genetic predisposition (e.g., the aldose reductase gene), increased oxidative stress, sorbitol accumulation or the deposition of advanced glycated end products in the lens. Studies have shown that the lens of a diabetic contains more sorbitol, glucose, and fructose than that of a nondiabetic23. Patients may present with reduced visual acuity, blurred vision, monocular diplopia or glare intolerance. Diabetics have also been reported to have higher incidence of cataract surgery, require surgery at an earlier age and end with worse visual outcome following surgery24.It has been estimated that up to fifteen per cent of cataract surgery is performed on diabetics25. The main indications for surgery are the same as for non-diabetic patients. In addition, surgery is indicated if the lens opacity prevents an adequate examination of the fundus or produces excessive scatter of light during laser therapy. Following surgery, the incidence of capsular opacification is greater in diabetics than in non-diabetics. Therefore it may be necessary to do a large YAG capsulotomy to improve vision or improve visualization of the retina. The results of surgery are worst in those eyes with active proliferative retinopathy26. Anterior Uveitis (AU) Anterior uveitis is characterised by acute ocular pain, redness of the eye, photophobia, ciliary injection, decreased visual acuity and dark floating spots in the vision. It may be anterior, posterior, or both, and there can be considerable ocular morbidity. Ophthalmology management may include cycloplegia, corticosteroids (topical / systemic) or corticosteroid-sparing immunosuppressive agents in refractory cases. Anecdotal evidence exists about the association between anterior uveitis (AU) and diabetes27. Many immunological reactions have been speculated to play a crucial role: the high levels of CD8 subsets found could be an expression of the unstable lymphocytic equilibrium. Whether or not uveitis in diabetic patients is a true inflammation rather than an ischemic phenomenon is still unknown. Treatment is usually simple. Dark glasses may be helpful. Steroid eye drops or ointment may be needed. Hara and others reported that acute bacterial infection in patients with diabetes mellitus may lead to hypopyon iritis.28 Optic nerve Diseases Optic nerve diseases of diabetic origin occupy a significant place in routine ophthalmologic practice and they are one of the most important complications of diabetes. The common optic-nerve diabetes-induced diseases are congenital bilateral optic nerve atrophy due to Juvenile IDDM, diabetic papillopathy, anterior ischemic optic neuropathy, posterior ischemic optic neuropathy, and retrobulbar neuritis. Possible etiopathogenetic mechanisms are analysed, the most important of which are hereditary, toxic, metabolic, ischemic and transudative ones. One of the essential characteristics of optic nerve diabetes- induced disease is that the optic nerve involvement is not always associated with evident signs of diabetic retinopathy. Also, in several cases, optic nerve disease preceded the occurrence of retinopathy29. Papillopathy (nonarteritic AION) Diabetics are susceptible to papillopathy which is characterised by acute disc oedema without the pale swelling of anterior ischemic optic neuropathy. Up to 25% of patients with nonarteritic AION had a history of diabetes. Layana and others reported a case of papillopathy as the first manifestation of diabetes30. It is bilateral in one half of cases and may not show an afferent pupil defect. The moderate loss of vision with papillopathy usually disappears spontaneously within 2-10 months with residual mild optic atrophy. Long-term visual prognosis depends on the presence of diabetic retinopathy and, very rarely, the progression of this papillopathy to anterior ischemic optic neuropathy31. There is a 6 months). Asteroid hyalosis Asteroid hyalosis (AS) is a benign condition characterized by small white or yellow-white spherical or disc shaped opacities throughout the vitreous. Major epidemiological studies confirm the association between AS and diabetes45. In patients undergoing cataract surgery, AS should be noted as artefactual lowering of axial length measurement can lead to significant error in calculations of intraocular lens power46. Usually no treatment is recommended for AS. Pars plana vitrectomy may be considered if these opacities interfere with the diagnosis and treatment of retinal disorders. Ocular motility disorders The neuro-ophthalmic manifestations of diabetes are diverse. Metabolic abnormalities due to hyperglycaemia, lack of insulin and their consequences and ischaemic phenomena secondary to diabetic microangiopathy account for nerve lesions47. In a study by Watanabe and colleagues48, 0.97% of patients with diabetes demonstrated cranial nerve palsies. Of these, 41% had 3rd nerve palsy. In contrast, only 0.13% of non-diabetic patients had any cranial nerve palsy. Concerning age, sex, the state of glycemic control, diabetic complications and method of treatment, there were no differences disclosed in the diabetic patients with cranial nerve palsy. Extraocular muscle palsy and diplopia may be caused by a mononeuropathy of cranial nerves 3, 4 or 6 from microinfarction of the nerves that involve ocular muscles. 3rd nerve palsy is most common and the eye is directed, down and out due to misalignment of the visual axes. Ptosis of the eyelid may preclude diplopia. In addition, pupillary dilatation can cause symptomatic glare in bright light (if the ptotic lid does not cover the pupil), and paralysis of accommodation causes blurred vision for near objects. Pupillary sparing in diabetic third nerve palsy is an important diagnostic feature, distinguishing it from more sinister causes such as intracranial aneurysm or tumour. When 4th nerve is involved, there is Hyper deviation (involved  eye is higher) as a result of  weakness of the superior oblique muscle. This is more obvious when the head is titled to the ipsilateral shoulder (Bielschowsky’s head tilt  test). In one population-based case-control study of isolated VI cranial nerve, patients with VI cranial nerve palsy were six times more likely to have diabetes than controls49. 6th nerve palsy manifests as defective abduction, which is caused by weakness of the lateral rectus with normal adduction. In the primary position, there is a convergent strabismus as a result of the unopposed action of the medial rectus. The face is turned into the field of action of the paralyzed muscle to minimize diplopia, so that the eyes are turned away from the field of action of the paralyzed muscle.Horizontal diplopia is worse in the field of action of the paralyzed muscle and least away from its field of action. Complete recovery usually occurs within 9 months. Refractive Errors Although refractive errors have been associated with diabetes in small series, there are few large epidemiological studies to confirm this association. Hyperglycaemia is a significant cause of transient refractive change in diabetic. Patients may present with decreased acuity and asthenopia. Transient hyperopic changes are highly dependent on the magnitude of plasma glucose concentrations50. The best hypothesis at this time remains the sorbitol production via the polyol pathway with overhydration of the lens. Although the alteration in refractive index in the lens may contribute to the hyperopic change, no change in lens or corneal biometrics has been observed. Interestingly, despite intensive medical treatment, a considerable number of patients become more hyperopic51. It is critical that correction of refractive errors (spectacles, contact lenses, various keratorefractive procedures) should be deferred until blood sugar levels are stable. Tritan color vision deficiencies Functional visual deficits can occur in patients with diabetes mellitus who show no visible morphological alterations in the retina52. Post-receptoral alterations of the inner retina at the preretinopic stage of diabetes causes a pattern of colour vision deficits and this is related to the duration of diabetes53. Lens opacity changes also play a large role as the age of the patient increases. Accommodative dysfunction Diabetics exhibit a high sensitivity for perception of optical defocus. The blood glucose levels influenced the extent and accuracy of accommodative responses. In a study by Kergoat and others, the accommodative precision in diabetics when compared to a group of nondiabetics in the same age range, showed evidence of being more reliant on target colors54. Visual field defects Visual field defects in diabetes result from subclinical microangiopathy. They occur more frequently in noninsulin-dependent patients than in insulin-dependent patients. They are often detected in patients with at most moderate retinopathy55. Diabetes may influence glaucomatous optic nerve damage and cause a difference in the pattern of visual field loss in patients with primary open-angle glaucoma56. Other ocular manifestations Diabetic iridopathy is one of the manifestations of diabetes in the anterior part of the eye. It exists even in the early stages of this disease and progresses in parallel with retinopathy. Clinical use of the flare-cell meter enables the quantitative assessment of blood-aqueous barrier function in diabetics57. Conclusion Diabetes mellitus is associated with a range of eye diseases, many of which are sight threatening or causing much anguish to the patient. A general practice ophthalmic screening model offers the potential to opportunistically "catch" unscreened diabetics presenting to the practitioner in a variety of alternate circumstances and would be cost-effective for both the patient and community. It would be prudent for the informed clinician to appropriately investigate, treat or refer patients appropriately to allow for early institution of effective therapy, which may potentially safe the patients’ sight and life. Prompt communication and referral to an ophthalmologist should always be considered where indicated. With motivation and support, clinicians can play a more active contribution in the domain of effective screening for diabetic eye diseases in the general population. Table 1: Diabetes and Cataract Source, year of publication Sample size Age (years): Mean (Range) Prevalence (%) Duration Of DM Type of diabetes related incidence Odds Ratio (OR), 95%Confidence Interval (CI) p-value Limitation of study Cohen DL et al58, 1991 188 - 29 - - - - Relation with mean age and duration of disease not studied Harding et al59, 1993 1940 50- 79 11 F>M - - F=4.3-14.3 M=2.05-5.71 - Relation with duration of disease not studied Klein et al.60, 1998 3684 65 (43 – 84) 70 - - 0.04 P < .001 Relation with hyperglycaemia not studied. Rowe et al.61., 2000 3654 73 (49- 97) 5.9 - - 1.8 (1.0-3.1) Past cataract surgery- 2.5 (1.5- 4.2) 0.05 Long term prevalence with indications and effect of surgery not included Janghorbani et al62, 2000 3606 49.2 10.4 M=13.6 F=8 7.6yrs IDDM=7.1 NIDDM=11.7 (i)and 17.8(n-i) 9-11.9 - - Hennis et al..63, 2004 3427 50.9 (40 – 84) 22.5 - 1.13 (1.06-1.20) P< .001 Prevention not investigated Mukesh et al.64, 2006. 3721 62.5 (40- 98) 6.9 - - 1.2 (0.7-2.1) P< .001 Study of modifiable risk factors incomplete. Needs future prospective study Table 2: Glaucoma and Diabetes Source, year of publication Sample size Age (years): Mean (Range) Prevalence (%) OR (CI) p-value Limitation of Study Conclusion Mitchell et al.65, 1997 3654 60.2 (49 -96) 16.7 2.82 (1.35- 5.87) 55) 1.5 3.11(1.12-8.66) /=5yrs:RR-1.54, 95%CI-0.9-2.62. Read More