Epiphora/Vascular Disease

From the 2009 Summer Conference, presented by the Utah Ophthalmology Society

Educational Objectives

The goal of this program is to improve the diagnosis and management of patients with epiphora or vasculopathy af­fecting the eye. After hearing and assimilating this program, the clinician will be better able to:

1.   Identify underlying causes of abnormal tearing.

2.   Describe diagnostic techniques for evaluation of
tearing.

3.   Explain treatment options for abnormal tearing.

4.   Recognize the scope of vascular disease affecting the eye.

5.   Identify indications for referral of patients with ocular manifestations of vascular disease.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning com­mittee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose.

Acknowledgments

Drs. Kim and Warner were recorded at the 2009 Summer Conference, presented August 7, 2009, in Deer Valley, UT, by the Utah Ophthalmology Society. The Audio-Digest Foundation thanks Drs. Kim and Warner and the Utah Ophthalmology So­ciety for their cooperation in the production of this program.

Epiphora: Evaluation and Management of the Tearing Patient

Chang Hee Kim, MD, Assistant Professor of Oculoplastic Surgery, John A. Moran Eye Center, University of Utah, School of Medicine, Salt Lake City

Case 1: 65-yr old Filipino man presented with complaint of tearing (left eye worse than right); worse since moving to Utah, when using computer, and on cold windy days; problem resolves when patient visiting Philippines; on exam­ination, telangiectasias and inspissated meibomian glands; few punctate erosions (left worse than right); rapid tear breakup time; diagnosis  —blepharitis and dry eye syndrome; treatment  —  nonsurgical; warm compress (rice in sock [place 1 cup uncooked rice in clean cotton sock; heat in microwave 25 sec]); baby shampoo scrubs; artificial tears; if tear film foamy, bacitracin ointment at bedtime to decrease colonization; for inflammation, stepwise progression (doxycycline, cyclosporin A [Restasis], topical azithromycin [usually at bedtime])

Case 2: 75-yr-old white female patient presented with episodic tearing in left eye; previous episode of pain and swell­ing in medial canthus; symptoms resolved with course of oral antibiotics; on examination, eyelids normal with nor­mal tear breakup time; obvious tear meniscus (right worse than left); diagnosis  —previous episode of dacryocystitis; now presenting with nasolacrimal duct obstruction; management  —  speaker would not dilate and ir­rigate while patient actively infected; antibiotic therapy only temporizing (once lacrimal sac or nasolacrimal duct scarred, problem will recur); definitive treatment external dacryocystorhinostomy with silicone stenting

Differential diagnosis: etiologies of tearing  —  overproduction; tear film instability causing premature evaporation; reflex tearing due to surface disease; eyelid malpositioned or unstable; punctal, canalicular, or nasolacrimal duct obstruction; patient history  —  discharge watery or purulent? constant or intermittent? burning foreign body sensa­tion suggests surface problem; situational (eg, tearing caused by mastication suggests aberrant cranial nerve regen­eration); onset with cold weather or fatigue suggests dryness; trauma; tumors (unusual); ask about previous facial or sinus surgery; clinical evaluation  —slit lamp examination to detect inspissated glands, telangiectasias, abnormal tear breakup time, epithelial erosions; trichiasis common cause of tearing; check for laxity of upper or lower eye­lids; determine punctal caliber; Schirmer test; dilation and irrigation

Synkinesis and aberrant cranial nerve regeneration: problem of overproduction; “crocodile tears” occur only while chewing food; treatment  —  botulinum toxin type A (Botox) applied to lacrimal gland; effective, but tempo­rary (lasts 2-3 mo); potential side effects include ptosis and diplopia

Floppy eyelid syndrome: index of suspicion increases if  —  patient obese; no obvious laxity in lower eyelid; tearing intermittent and worse in morning; upper lid everts with minimal tension; more diagnostic tips  —  as average body mass index (BMI) continues to increase, incidence expected to increase; symptoms include morning pain, irritation and discharge; eyelid everts while patient sleeping; chronic conjunctivitis caused by conjunctiva and tarsus rubbing against bedding; medical options  —  weight loss; ocular lubrication; shield to prevent eversion of eyelid while sleep­ing; surgical  —  eyelid tightening procedure (full-thickness wedge resection)

Ectropion

Case: eversion of eyelid margin; punctal malpositioning; chronic exposure of conjunctiva, causing keratinization; if severe enough, exposure keratopathy develops

Types: involutional  —  most common; horizontal laxity (especially at lateral canthal tendon); cicatricial  —  history of eyelid or cheek tumor; atopic dermatitis around eyelids; facial burns; paralytic  —  from stroke, Bell’s palsy, or neurosurgical procedures (especially involving facial nerve tumors or acoustic neuromas)

Lateral canthal tendon laxity: patient may present with C- or V-shaped canthus; treatment  —  lateral tarsal strip (LTS), and/or canthoplasty

Tarsal plate eversion: so much laxity that tone of orbicularis pulls eyelids forward; case  —  tarsus bright red; skin lax and loose (unlike cicatricial entropion); treated with repair of dehisced retractor band and LTS; significant im­provement 2 wk later

Treatment of ectropion

Medical: artificial tears and ointments to decrease irritation

Surgical: involutional  —  LTS; cicatricial  —  lamellar lengthening (skin grafting); paralytic  —  cheek lift; use of spacer graft; horizontal tightening procedure; in severe or urgent cases, tarsorrhaphy recommended

Entropion: inversion of eyelid margin associated with trichiasis and punctal malposition; 3-fold problem (horizontal laxity; dehiscence of retractor bands; in some cases, overriding orbicularis); in developing world, trachoma fre­quent problem; involutional  —  forceful blink may elicit inversion; treatment LTS and retractor band repair; cicatricial  —  facial fractures from car accident required repair (transconjunctival approach for open reduction and internal fixation [ORIF]); healed with some scarring; posterior lamellar lengthening with porcine collagen (Endur­agen) graft performed

Punctal stenosis: puncta atrophic; causes include use of mitomycin C and (most commonly) docetaxel (Taxotere [breast cancer therapy]); over time, puncta become keratinized; vary in appearance and size, but some not stenotic ; punctoplasty (some use Vannas scissors; speaker prefers Kelly-Descemet membrane punch); case  —  man fell on farm implement; treatment insertion of Jones Pyrex tube or conjunctival dacryocystorhinostomy (DCR)

Nasolacrimal duct obstruction: diagnosis  —  create supraphysiologic pressure by cannulating and irrigating; if pa­tient senses saline solution at back of throat, incomplete or functional blockage indicated; reflux through upper puncta sign of complete blockage; etiologies  —  congenital; involutional; previous dacryocystitis; sinus disease; trauma; tumor; in children  —most common cause imperforate valve of Hasner; may resolve spontaneously; probe and intubation may be indicated in patients ³1 yr of age; in adults  —  rarely resolves spontaneously (treatment surgi­cal); surgical treatment  —  DCR to create communication between lacrimal sac and nasal mucosa; silicone intuba­tion and stenting in place 2 to 4 mo; anatomic success rate ³90%

Vasculopathies Affecting the Eye and Brain

Judith E.A. Warner, MD, Associate Professor of Ophthalmology and Neurology, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City

Atherosclerosis Risk in Communities (ARIC; study by Wong, 2002)

Objective: to examine relationship between white matter lesions (WMLs), retinal microvascular abnormalities, and incident stroke in healthy, middle-aged men and women

Study design: 1684 subjects 51 to 72 yr of age who had magnetic resonance imaging (MRI) and retinal photogra­phy; MRI graded 0 (no WMLs) to 9 (all white matter involved); later, subjects regrouped as having 1) few or no WMLs, or 2) significant WMLs; WML status correlated with presence of  —microaneurysms, retinal hemor­rhages, and soft exudates; arteriovenous (AV) nicking; focal anterior narrowing; arteriole-to-venule ratio (AVR)

Results: patients with retinopathy more likely to have WMLs than those without; the more WMLs seen onMRI, the more likely retinal abnormalities; 5-yr incidence for stroke  —  1.4% if no WMLs or retinopathy; 4.0% with WMLs; 4.7% with retinopathy; 20.0% with retinopathy and WMLs; relative risk for stroke  —  2 to 3 times higher with WMLs; almost 4 times higher with retinopathy; 18 times higher with both

More systemic findings associated with retinopathy

Retinal microvascular abnormalities and cardiovascular abnormalities (Wong, 2003): looked at participants in Bea­ver Dam Eye Study; retinopathy independently associated with cardiovascular (CV) mortality

Retinal vascular changes and lower extremity amputations in diabetics (Wong, 2003): retinopathy strongly associ­ated with lower extremity amputation (increases risk 3-fold)

Retinal microvascular signs and risk for stroke (Mitchell, 2005): looked at participants in Blue Mountains Eye Study; even in nondiabetics, microaneurysms or retinal hemorrhages increased risk for stroke

Retinal microvascular abnormalities and subclinical cerebral infarction (Cooper, 2006): retinal changes and MRI-defined stroke associated in hypertensives

Retinal vessel diameters and risk for stroke (Ikram, 2006): larger retinal venular diameters (not smaller arteriolar diameters) associated with increased risk

Retinal microvascular signs, cognitive function, and dementia (Baker, Wong et al, 2007): retinopathy associated with poorer cognitive function (in hypertensives, associated with dementia)

Caveat: in meta-analyses, associations less consistent (except microvascular retinopathy and increased risk for stroke in hypertensive and normotensive individuals); many retinal abnormalities (eg, macroaneurysms, hemor­rhages, vascular abnormalities) may be associated with stroke; additional value of retinal examination not clear

Bottom line: fundus examination can be life-saving diagnostic procedure

Hereditary Retinal Vasculopathies (HRVs)

Grand syndrome: cerebroretinal vasculopathy (CRV); rare; presents in fifth or sixth decade of life; all patients have retinal vasculopathy and pseudotumor

Ophthalmic findings: blurred vision (but vision relatively preserved); microvascular changes in posterior pole; late signs include preretinal hemorrhages due to neovascularization; anatomic changes  —  enlarged foveal avascular zone; microaneurysmal dilation of capillaries; parafoveal telangiectasia; capillary obliteration; pathology  —  scattered microinfarctions

Neurologic findings: 10 of 18 patients had brain tumors; focal deficits, headaches, and signs of elevated intracranial pressure; anatomic changes  —  frontal lobe edema; mass lesions seen on computed tomography (CT; all frontopa­rietotemporal and confined to white matter); CRV  —  obliterative fibrosis; proliferative clusters of small vessels and telangiectatic vascular dilatation

Hereditary endotheliopathy retinopathy, nephropathy, and stroke (HERNS) syndrome: Jen, 1997  —  Chinese-American family with onset of visual loss in 20s and 30s; followed 4 to 10 yr for subsequent development of focal neurologic deficits; signs and symptoms include renal dysfunction and migraine; ophthalmic findings  —  scotomata, macular capillary dropout, dilatation, microaneurysms, and telangiectasia; neurologic findings  —  presymptomatic psychiatric disturbance; focal deficits; abnormal MRIs; with focal deficit, contrast-enhancing lesions seen; MRI (case)  —  at 32 yr of age, visual complaints only (MRI normal); at age 42 yr, prominent white matter disease (rapid progression seen 1 yr later); most often in frontoparietal region (may be misdiagnosed as brain tumor); pathology shows subacute infarct with multilayered appearance of capillary membrane

Autosomal dominant vascular retinopathy, migraine, and Raynaud’s phenomenon (Terwindt syndrome): anal­ysis of large Dutch family  —  no brain tumor or neurologic deficit; 80% of patients with HVR had Raynaud phenom­enon (70% have migraine; 55% have both); vision relatively preserved; youngest patients asymptomatic; capillary occlusions in third and fourth decades of life; retinal artery occlusions in fifth decade; proliferative retinopathy de­velops later in life

Genetic findings (Ophoff, 2001): Terwindt syndrome, Grand syndrome, and HERNS mapped to single locus on chromosome 3p21.1-21.3; HVR common feature

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukocephalopathy (CADASIL): first described in 1977; associated gene identified on chromosome 19; pathology  —  granular osmophilic material in basement membrane of smooth muscle cells; clinical clues  —  lesions confined to central nervous system (CNS); re­current subcortical white matter infarcts develop in adulthood and cause stepwise decline (leading to dementia and death); look for family history; no spinal cord or optic nerve head involvement; ophthalmic findings (case)  —  retinal arteriolar changes on funduscopic examination; vision normal; attenuated and sheathed vessels in nasal re­gion of both retinas; optic nerve normal; patchy hyper- and hypofluoresence; more findings  —microinfarcts and hemorrhages; small AVR; retinal cotton wool spots (CWS)

Idiopathic/Infectious Vasculopathy

Susac syndrome: recognized as syndrome in 1979; triad of microangiopathy in brain, retina, and cochlea; clinical clues  —  broad age-range of onset; 80% of affected patients women; most patients do not have full triad at presenta­tion (can take weeks or years to develop triad); disease active 2 mo to 11 yr; ophthalmic findings  —  branch retinal artery occlusions (usually bilateral); rarely, periarteriolar inflammation or sheathing; arterial wall hyperfluores­cence and narrowing of nonoccluded vessels; cochlear findings  —  end artery stroke; possible hearing loss, vertigo, and “rumbling” tinnitus; low-to-mid frequency hearing loss key; neurologic findings  —  encephalopathy, memory loss, headache, and focal deficits; on MRI, “snowballs” seen in corpus callosum; inflammation in cerebrospinal fluid (not cellular inflammation); pathology  —  microinfarcts in brain; antiendothelial cell injury

Eale’s disease: clinical clues  —  affects young men (often purified protein derivative (PPD)-positive); ophthalmic findings  —floaters and decreased vision; bilateral and often symmetric; primarily venous disease that leads to clas­sic funduscopic findings; venous staining without sheathing; neurologic involvement  —not uncommon (eg, myelop­athy, spinal cord infarcts, seizure, stroke)

HIV-associated vasculopathy: often asymptomatic; patient may have color or contrast sensitivity defects; likelihood increases with decreasing CD4 count; linear morphology of HIV-associated CWS distinct from that in diabetic pa­tients; intraretinal hemorrhages common; in 1993 study by Geier, associated with poor perfusion to brain

Multiple sclerosis (MS): associated with pars planitis, ocular inflammation, and venous sheathing; chronic relapsing or remitting disease (in some cases, progressive); usually does not destroy vision; histopathology  —  lymphoplasmacytic infiltrate around retinal vessels; pars planitis  —  inflammatory condition of peripheral retina and ciliary body; occurs in 2% to 20% of patients with MS (in recent studies, 11%-33% of patients with pars plani­tis had MS); pars planitis with cystoid macular edema treatable

Suggested Reading

Baker ML et al: Retinal microvascular signs, cognitive function and dementia in older persons: the Cardiovascular Health Study. Stroke 38:2041, 2007; Cooper LS et al: Retinal microvascular abnormalities and MRI-defined subclinical cerebral in­farction: the Atherosclerosis Risk in Communities Study. Stroke 37:82, 2006; Dastur DK, Singhai BS: Eales’ disease with neu­rologic involvement. Part 2. Pathology and pathogenesis. J Neurol Sci 27:323, 1976; Geier SA et al: Brain HMPAO-SPECT and ocular microangiopathic syndrome in HIV-1 infected patients. AIDS 7:1589, 1993; Grand MG et al: Cerebroretinal vasculopa­thy. A new hereditary syndrome. Ophthalmology 95:649, 1988; Jen J et al: Hereditary endotheliopathy with retinopathy, ne­phropathy, and stroke (HERNS); Mitchell P et al: Retinal microvascular signs and risk of stroke and stroke mortality: a population-based case-control study. Ophthalmology 110:933, 2003; O’Halloran HS et al: Microangiopathy of the brain, retina and cochlea (Susac syndrome). A report of five cases and a review of the literature. Ophthalmology 105:1038, 1998; Robinson W et al: Retinal findings in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cada­sil). Surv Ophthalmol 45:445, 2001; Rolinski B et al: Endothelin-1 immunoreactivity in plasma is elevated in HIV-1 infected patients with retinal microangiopathic syndrome. Clin Investig 72:288, 1994; Terwindt GM et al: Clinical and genetic analysis of a large Dutch family with autosomal dominant vascular retinopathy, migraine and Raynaud’s phenomenon. Brain 121:303, 1998; Wong TY et al: Cerebral white matter lesions, retinopathy, and incident clinical stroke. JAMA 288:67, 2002.