Thyroid Ophthalmopathy (Graves' Disease) Signs and Symptoms Thyroid eye disease, Graves' ophthalmopathy, dysthyroid ophthalmopathy, and Graves' disease are all synonymous terms connoting a process clinically characterized by eyelid retraction, proptosis, conjunctival exposure, ocular injection, ocular chemosis, corneal compromise, extraocular muscle infiltration and fibrosis with the potential for compressive optic neuropathy. It is the most common cause of bilateral, symmetric proptosis in adults. Interestingly, ocular findings may occur independently from dysthyroid function. Euthyroid Graves' disease is a condition where the characteristic ophthalmic manifestations of thyroid eye disease exist in the presence of a clinically and biomedically normal thyroid gland. Most patients with ocular Graves' disease manifest systemic hyperthyroidism. Up to 80 percent of patients with systemic hyperthyroidism develop some eye signs. Systemic signs of hyperthyroidism include weight loss despite increased appetite, nervousness, palpitations, tachycardia while at rest, systemic hypertension, and hyperreflexia. Conversely, lethargy, bradycardia and weight gain despite decreased appetite are signs of hypometabolism and potential hypothyroidism. In 1969, the American Thyroid Association adopted the formal classification of Ocular Graves' disease, represented by the pneumonic NOSPECS. The disease process passes through 6 stages: (0) No signs or symptoms present, (I) Only symptoms of ocular irritation (dryness, tearing, foreign body sensation), (II) Soft tissue involvement (periorbital edema), (III) Proptosis, (IV) Extraocular muscle involvement (ophthalmoplegia), (V) Corneal involvement (dense punctate epitheliopathy, infiltration and ulceration), (VI) Sight loss with or without visual field compromise secondary to compressive optic neuropathy. However, because the disease is recognized as variable, the formal classification was revised in 1974 to range from no manifestations to mild, moderate or severe manifestations. The common, clinically diagnostic eye signs include: von Graefe's sign (superior lid lag upon down gaze), Dalrymple's sign (eyelid retraction), Stellwag's sign (infrequent blinking), and Ballet's sign (palsy of one or more extraocular muscles). Pathophysiology Graves' disease is a multisystem disorder of unknown etiology, characterized by one or more of the following three clinical entities: (1) hyperthyroidism associated with diffuse hyperplasia of the thyroid gland; (2) infiltrative ophthalmopathy; and (3) infiltrative dermopathy (pretibial myxedema). The histopathologic features of the malady include an infiltration of the thyroid gland, skin, extraocular muscles and orbital fat by lymphocytes, macrophages, plasma cells, mast cells and mucopolysaccharides. These changes are characteristic of, but not limited to, an immunologically mediated mechanism. Management The diagnosis of Graves' disease can often be made easily based on symmetrical exophthalmos (exophthalmometry >22mm or asymmetry greater than 3mm) and lid retraction in the presence of known hyperthyroidism. If symptoms are present and a systemic etiology has not been investigated, consultation with an endocrinologist and laboratory testing for thyroid hormones T3 (triiodothyronine), T4 (tetra-iodothyronine) and TSH (thyroid stimulating hormone) are indicated. Neuroimaging of the orbits in patients with exophthalmos and positive forced duction testing allows clinicians to distinguish extraocular muscle infiltration from inflammatory or infectious myositis. The systemic management of patients with ocular Graves' disease lies in the domain of the endocrinologist. Agents that block the synthesis of thyroid hormone such as propylthiouracil (Tapazole) or decrease hypermetabolic symptoms such as propranolol (Inderal) have been proven effective. Systemic steroids, immunosuppressive agents like azathioprine, cyclosporin or cyclophosphamide in combination with orbital irradiation have shown promise in advanced cases. Today, surgical orbital decompression procedures are a last resort. Since the primary concern proptosis and lid retraction presents is corneal exposure, ocular management is predominantly supportive. Typically, moistening the cornea with artificial tear drops and ointments is effective. Moisture shields that can be attached to the temples of spectacles help to preserve tears and retard tear evaporation. Punctal occlusion may be effective. Cases that involve moderate to severe keratopathy may require prophylactic topical antibiotics. Visual fields should be performed on patients with advanced stage disease, monitoring for the first sign of sight or field loss. Evaluation is usually every three to six months and is based upon severity.

POSTERIOR VITREOUS DETACHMENT

SIGNS AND SYMPTOMS
The patient, usually over the age of 50, will present with a sudden onset of floaters. There is usually one floating spot that is especially large and troublesome to the patient and serves as the impetus to seek immediate care. There may also be associated photopsia if the patient is experiencing vitreoretinal traction. If the patient presents with multiple floaters, there may be an associated vitreous hemorrhage, especially if there is an associated reduction in visual acuity. Patients who report diffuse floaters during routine examination usually are suffering from benign vitreous syneresis and not posterior vitreous detachment.

PATHOPHYSIOLOGY
The vitreous is comprised of collagen fibrils and glycoaminoglycans, supported by hyaluronic acid molecules. With aging, reduction in hyaluronic acid causes loss of support to the collagen. The vitreous may collapse, with detachment of the posterior hyaloid face from the optic disc. This usually is observable ophthalmoscopically as an annulus floating in the vitreous over the posterior pole. As the vitreous detaches peripherally, areas of vitreoretinal adhesion may result in a tear in the sensory retina with the ensuing possibility of a rhegmatogenous retinal detachment. If the tear bridges a blood vessel, a vitreous hemorrhage ensues.

MANAGEMENT
A PVD found asymptomatically on routine examination is benign, but requires monitoring yearly. A patient who presents with a sudden onset PVD without retinal breaks or hemorrhage requires repeat peripheral examination in six weeks, as the risk of retinal complications is highest within the six weeks following vitreous detachment. If no retinal breaks are seen at that point, routine yearly examination is all that is needed. Prophylactically treat any fresh breaks associated with a new PVD immediately with photocoagulation or cryoretinopexy

MACULAR DEGENERATION

SIGNS AND SYMPTOMS
Age-related macular degeneration (AMD) is the leading cause of legal blindness in the United States of America for persons over the age of 65. AMD is present in approximately 10 percent of the population over the age of 52 and in up to 33 percent of individuals older than 75. AMD is an extension of abnormalities that begin and progress through Bruch's membrane, involving the retinal pigment epithelium (RPE) and photoreceptors. The earliest clinical manifestation of AMD are drusen and macular pigmentary atrophy. The presence of drusen does not indicate AMD. However, it serves as precursor, warning that there is the potential for progression and visual loss. AMD is bilateral in 55 percent of cases.

The visual symptoms associated with AMD depend on its severity and type. In general, the "dry" form (no subretinal choriodal neovascularization, exudation or hemorrhage) is less severe, producing a gradual, painless distortion or loss of central vision. Some patients complain of color distortion. "Wet" AMD (subretinal choriodal neovascularization, exudation and or hemorrhage) often produces severe central visual loss. Visual loss produced by wet AMD is often rapidly progressive.

Some of the clinical retinal signs of dry AMD include drusen of the posterior pole, granular clumping and disorganization of the RPE in the macular area, macular RPE hyperplasia and degeneration of the outer retinal layers with circumscribed areas of geographic atrophy of the RPE.

Some of the clinical retinal signs associated with wet AMD include hard and soft drusen, subretinal thickening secondary to classic or occult choroidal neovascularization (producing a grayish-green subretinal hue), subretinal, intraretinal or vitreous hemorrhage, subretinal and intraretinal exudation with serosanguinous fluid accumulation and fibrovascular scar formation (disciform scarring).

PATHOPHYSIOLOGY
All forms of AMD possess initial, common changes within the macular RPE. While the mechanisms and processes are poorly understood, some postulate these changes are initiated by isolated regions of choriocapillaris vascular failure. These proceedings cause the RPE to degenerate, resulting in photoreceptor loss. As the photoreceptors disintegrate, the inner nuclear layer collapses and contacts Bruch's membrane, initializing the degeneration of the outer retinal layers. Some theorize that the mechanism of damage may be through ultraviolet radiation-induced oxidation and free radical formation within these structures.

Wet AMD results when the macular RPE/Bruch's barrier is compromised by new, weak and leaky blood vessels that grow upward into the retina from the choriocapillaris. These occult (poorly defined) or classic (more easily defined) subretinal choroidal neovascular membranes may leak serosanguinous fluid causing RPE detachment, sensory retinal detachment, subretinal or intraretinal bleeding or fibrovascular, disciform scarring.

MANAGEMENT
Begin managing patients with potential or diagnosed AMD by recognizing the associated risk factors and providing patient education. The disease is more common in individuals who have a family history of AMD, are of light complexion, in those who have a cardiovascular history, history of previous lung infection, hyperopia or decreased hand grip strength. It is typically more progressive in males. Smoking is a significant risk factor.

The management of patients with dry AMD begins with biannual eye examination, with dilated funduscopy. Home therapy, aimed at early detection, using a home Amsler grid may work to monitor the stability of suspicious or involved maculae. The elimination of potentially harmful ultraviolet light using UV coatings on spectacles and sunglasses may also reduce the risk of photochemical /oxidative damage to the retina for all patients.

Researchers have indicated that oral antioxidants like vitamins C and E and oral zinc may play a role in reducing retinal damage by terminating the chemical reactions initiated by free radicals, created by retinal metabolism. Multiple vitamins, oral zinc or products specifically designed for this purpose, such as Ocuvite and ICaps, are useful as a tool for slowing the progression of AMD.

The treatment for symptomatic wet AMD begins with a referral to the vitreoretinal specialist for intravenous fluorescein angiography. The Macular Photocoagulation Study (MPS) examined the efficacy of treating subretinal, extrafoveal (200 to 2,500 µm from the center of the foveal avascular zone, juxtafoveal (1 to 200 µm from the center) and subfoveal choroidal neovascular membranes with laser photocoagulation. Laser photocoagulation reduces the risk of severe vision loss in patients with definable subretinal choroidal neovascular membranes.

In cases where hemorrhage and exudate obscures the angiogram or the neovascular membrane is poorly defined by fluorescein angiography, indocyanine green angiography may offer an additional modality to determine if treatment is feasible. Unfortunately, the recurrence rate following treatment is approximately 50 percent. Most recurrences develop within the first year, making a three-month follow up schedule critical. The efficacy and effectiveness of surgical procedures for the removal of subretinal neovascular membranes are currently under investigation.

In cases where bilateral central visual acuity has been lost, low vision and vision rehabilitation specialists may be able to offer training or optical devices which improve patients' quality of life. Macular translocation surgery has been performed with significant success and restored usable vision to patients with wet ARMD.

RETINAL DETACHMENT

SIGNS AND SYMPTOMS
There are three forms of retinal detachment:

1. Rhegmatogenous retinal detachment (RRD), which results from a retinal break. The vast majority of rhegmatogenous detachments are symptomatic, with patients reporting photopsiae, floating spots, peripheral visual field loss, central blurring of vision or metamorphopsia.

2. Exudative or serous retinal detachment (ERD), which results from fluid accumulation under the sensory retina without a retinal break. Exudative detachments do not generally present with photopsiae but may be associated with moderate vision loss, metamorphopsia or a visual field deficit.

3. Tractional retinal detachment (TRD), which results from the pull of proliferative fibrovascular vitreal strands. Tractional detachments are typically asymptomatic unless central vision is threatened, in which case the patient can suffer severe and abrupt vision loss.

In cases of extensive unilateral retinal detachment, you may observe a relative afferent pupillary defect. Intraocular pressure may be reduced in eyes with acute retinal detachment.

Ophthalmoscopy in cases of RRD usually reveals a clumping of pigment cells within the anterior vitreous (Shaffer's sign). There may be an area of white or grayish elevated retina adjacent to the instigating retinal break. If a significant area of the retina is involved, you may note a milky, lackluster appearance with undulating retinal folds.

A rhegmatogenous detachment will not change position with changes in body posture, however it may shift and then return to its original orientation with quick eye movements. Associated findings may include posterior vitreous detachment and preretinal or vitreal hemorrhage. Retinal pigment epithelial hyperplasia may be noted in cases of long-standing retinal detachment (pigment demarcation line), and is a good prognostic feature.

ERD appears clinically as a focal, serous elevation of the retina, which shifts position with changes in posture and eye movement. The subretinal fluid obeys gravity, always affecting the lowest aspect of the eye. Ophthalmoscopy reveals a smooth, translucent, dome-shaped protrusion of the retina. There are usually no hemorrhages, except in cases of associated retinal vasculopathy.

TRD is always associated with vitreal strands and membranes. It appears as a concave, smooth-surfaced detachment with marginal fibrovascular bands emanating into the vitreous body. It is sometimes difficult to assess where the necrotic retina ends and the vitreal membranes begin. Very often, this area encircles an intact posterior pole, resulting in a retinal "pseudo-hole." TRDs are dense and immobile. This motility lends itself well to ancillary testing with ultrasonography.

PATHOPHYSIOLOGY
All retinal detachments involve the sensory retina dissecting from the underlying pigment epithelial layer by subretinal fluid. In rhegmatogenous detachments, this fluid is liquefied vitreous, which accesses the subretinal space via a retinal break. In exudative detachments, the fluid is derived from the choroid, passing through a defective Bruch's membrane. The origin of the subretinal fluid in tractional detachments is unknown. Both passive and active movement of subretinal fluid induce progression of retinal detachments, leading to partial or total loss of vision in some patients.

Retinal breaks are the predisposing factor in patients with rhegmatogenous detachment. These may result from preexisting conditions or ocular trauma. Some of the more common entities associated with RRD include lattice degeneration, flap tears, atrophic holes, operculated retinal breaks, and acquired retinoschisis with both inner and outer holes. As the retinal tissue loses its connection to the RPE, it becomes edematous and dysfunctional. Without surgical intervention, death of this tissue occurs within 48 to 72 hours.

Exudative detachments are relatively rare, occurring in association with subretinal disorders that damage the RPE layer. These may include choroidal neoplasms, Vogt-Koyanagi-Harada syndrome, posterior scleritis, congenital optic disc anomalies (optic pits, morning glory syndrome, etc.), Coat's disease and uveal effusion syndrome.

Transudation of fluid through the RPE defects causes detachment of the otherwise normal sensory retina. As the fluid shifts with eye and head movements, the involved portion of the retina changes. This explains why most patients with ERDs suffer significantly less devastating visual compromise than those with RRDs or TRDs.

Tractional detachments occur only in proliferative vitreoretinopathies. The most common of these is proliferative diabetic retinopathy, but many TRDs are associated with ischemic retinal vein occlusions, sickle cell retinopathy, retinopathy of prematurity, toxocariasis and trauma.

The etiology of TRD involves fibrotic scaffolding of the vitreous along proliferative vascular networks which induce strong anterior tractional forces through vitreal shrinkage. These forces induce the sensory retina to separate from the underlying RPE.

Unlike rhegmatogenous or exudative detachments which tend to be abrupt, TRDs are often slow and insidious, progressing at the same rate as the associated fibrovascular proliferation. Peripheral TRDs are therefore rarely if ever noticed by the patient. Macular TRDs, on the other hand, tend to be symptomatic, unless the underlying disease process has already compromised visual acuity.

MANAGEMENT
Patients presenting with an acute onset rhegmatogenous detachment that involves or threatens the macula warrant immediate retinal specialist consultation. All other fresh RRDs should be repaired within 24 to 48 hours; chronic or long-standing RRDs requiring treatment should be addressed within one week of diagnosis. While small retinal breaks or atrophic holes may be managed with laser photocoagulation or cryopexy, true retinal detachments require surgical repair.

Treatment options for RRD include scleral buckling procedures, pneumatic retinopexy and intraocular silicone oil tamponade. Most practitioners are familiar with scleral buckling procedures, the traditional surgery for retinal detachment. The retinal tear is first repaired with cryopexy, and the subretinal fluid is drained via a small scleral incision. Then, under general anesthesia, a soft silicone sponge or hard silicone band is used to indent the eye at the point of detachment, or to encircle the eye if the detachment is significant. This explant is sutured into place to reestablish adhesion between the sensory retina and RPE.

In pneumatic retinopexy, an intravitreal gas bubble (usually perfluoropropane, C3F8) serves to reattach the retina. This technique, performed under local anesthesia, is more common for treating smaller, superiorly located detachments. Cryopexy is performed at the site of the break, and then the gas is injected into the vitreal cavity. Careful eye and head positioning are important postoperatively to ensure resolution.

In certain instances, silicone oil tamponade may be favorable to either of these techniques. This procedure is identical to pneumatic retinopexy except that silicone oil replaces the expansive gas. (Silicone oil tamponade was actually used prior to the advent of pneumatic retinopexy, however the former has fewer applications and is therefore done less frequently.) Silicone oil tamponade is most commonly used to repair RRD resulting from cytomegalovirus infection in AIDS.

Exudative detachments, because of their nature, require intervention less often than do RRDs. ERDs will usually resolve spontaneously with appropriate management of the underlying condition. This may involve high-dose steroids in the case of inflammatory disorders, or radiation therapy and/or local resection in the case of intraocular neoplasms.

Because of their progressive nature, tractional detachments are typically more difficult to manage than either RRDs or ERDs. For this reason, intervention is often not attempted unless the macula is involved or threatened. Surgical repair of TRD usually involves pars plana vitrectomy. Silicone oil tamponade is another popular technique for the treatment of tractional detachments.

Herpes Zoster Ophthalmicus SIGNS AND SYMPTOMS Herpes zoster ophthalmicus (HZO) typically presents with nondescript facial pain, fever and general malaise. About four days after onset, a vesicular skin rash appears along the distribution of the fifth cranial nerve, characteristically respecting the vertical midline. The vesicles will discharge fluid and begin to scab over after about one week. The pain is extreme during the inflammatory stage, and patients are tremendously symptomatic. Ocular involvement may include follicular conjunctivitis, epithelial and/or interstitial keratitis, dendritic keratitis, uveitis, scleritis or episcleritis, chorioretinitis, optic neuropathy, and even neurogenic motility disorders (especially fourth cranial nerve palsy). If you see vesicles at the tip of the nose (known as Hutchinson's Sign), there is a 75 percent likelihood of ocular sequelae. PATHOPHYSIOLOGY HZO occurs when the trigeminal ganglion is invaded by the herpes zoster virus, a varicella-type virus which is usually referred to as "chicken pox" in children or "shingles" in adults. The virus remains dormant in trigeminal nerve cells, and can become reactivated years later by a reduction in the immune system. Neuronal spread of the virus occurs along the ophthalmic (1st) and less frequently the maxillary (2nd) division of the fifth cranial nerve. Vesicular eruptions occur at the terminal points of sensory innervation, causing extreme pain. Nasociliary involvement will most likely cause ocular inflammation, typically affecting the tissues of the anterior segment. Contiguous spread of the virus may lead to the involvement of other cranial nerves, resulting in optic neuropathy (cranial nerve II) or isolated cranial nerve palsies (cranial nerve III, IV or VI). MANAGEMENT The systemic component of this disorder is best treated with oral acyclovir, (Zovirax), 600 to 800mg five times a day for seven to 10 days, starting as soon as the condition is diagnosed. Recently, famciclovir (Famvir) 500mg p.o. t.i.d. has been shown to be as effective in treating herpes zoster ophthalmicus as acyclovir 800mg fives times per day. Timing is crucial, however, to avoid post-herpetic neuralgia. To achieve maximal benefit from oral anti-viral medications, you must start therapy within 72 hours of vesicular eruption. Otherwise, the patient is at risk for developing post-herpetic neuralgia and the beneficial effects of oral anti-viral therapy are lost. You may also wish to prescribe oral steroids to alleviate pain and associated facial edema. If so, try 40 to 60mg of prednisone daily, tapered slowly over 10 days. To treat the skin lesions, applying an antibiotic-steroid ointment, such as Pred-G, to the affected areas twice daily, may help. Ocular management depends on the severity and tissues involved. In most cases which involve uveitis or keratitis, use cycloplegia (homatropine 5% t.id./q.i.d. or scopolamine 0.25%) b.i.d./q.i.d. After ruling out herpes simplex, it's also possible to prescribe a topical steroid such as Vexol or Pred Forte q2-q.h. In any compromised eye, prophylaxis with a broad-spectrum antibiotic is a good idea. Finally, palliative treatment consisting simply of cool compresses, and oral analgesics in extreme cases, can be comforting. Cimetidine 400mg p.o. b.i.d may provide some additional relief from the neuralgia; why this works is not entirely understood.

Bacterial Conjunctivitis SIGNS AND SYMPTOMS Patients with bacterial conjunctival infections present with injection of the bulbar conjunctiva, episcleral vessels and perhaps papillae of the palpebral conjunctiva. The infection often starts in one eye, then soon spreads to the other. There will be thick mucopurulent discharge, and patients usually say that their eyelids and eyelashes are matted shut upon awakening. There may be mild photophobia and discomfort, but usually no pain. Visual function is normal in most cases. PATHOPHYSIOLOGY The eye has a battery of defenses to prevent bacterial invasion. These include bacteriostatic lysozymes and immunoglobulins in the tear film, the shearing force of the blink, the immune system in general, and non-pathogenic bacteria that colonize the eye and compete against external organisms that try to enter. When any of these defense mechanisms break down, pathogenic bacterial infection is possible. Invading bacteria, and the exotoxins they produce, are considered foreign antigens. This induces an antigen-antibody immune reaction and subsequently causes inflammation. In a normal, healthy person the eye will fight to return to homeostasis, and the bacteria will eventually be eradicated. However, an extra heavy load of external organisms can be too difficult to fight off, causing a conjunctival infection and setting the eye up for potential corneal infection. The most commonly encountered organisms are Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae and Pseudomonas aeruginosa. In cases of hyperacute bacterial conjunctivitis, the patient will present with similar signs and symptoms, albeit much more severe. The most common infectious organisms in hyperacute conjunctivitis are Neisseria gonorrhoeae and Corynebacterium diptheroides. There is more danger in hyperacute bacterial conjunctivitis as these organisms can penetrate an intact cornea. MANAGEMENT Ordering cultures and sensitivity tests is ideal for diagnosis but usually impractical and expensive. Most clinicians immediately begin treatment with a broad spectrum antibiotic and reserve culturing for hyperacute conditions or those that fail to respond to the initial therapy. There are many antibacterial options. Excellent initial broad spectrum antibiotics include Polytrim (polymixin B sulfate and trimethoprim sulfate), gentamicin 0.3%, and tobramycin 0.3%. These will give good coverage of gram-positive and gram-negative organisms, though the aminoglycosides (gentamicin and tobramycin) have weak activity against Staphylococcal species; there are also resistant strains of Pseudomonas. Fluoroquinolones such as Ciloxan, Ocuflox and Chibroxin are also excellent options. Therapy should be aggressive, with administration from QID to Q1H for the first few days. Although antibiotics will eradicate the bacteria, they will do nothing to suppress the concurrent inflammation. If there is no significant corneal disruption, prescribe a steroid such as Pred Forte, Vexol or Flarex along with your antibiotic of choice, or a steroid-antibiotic combination such as Maxitrol (neomycin, polymyxin B, dexamethasone 0.1%), Pred-G (gentamicin 0.3%, prednisolone acetate 0.1%), or Tobradex (tobramycin 0.3%, dexamethasone 0.1%).