Ординатура / Офтальмология / Английские материалы / Oxford American Handbook of Ophthalmology_Tsai, Denniston, Murray_2011

706 CHAPTER 22 Therapeutics

Systemic corticosteroids: general

Indications and mechanism

In severe ophthalmic inflammation, systemic corticosteroids may be required. Corticosteroids are anti-inflammatory but at higher doses are immunosuppressive. The immunosuppressive role of corticosteroids is via inhibition of NF-kB transcription factor signaling, thus blocking the production of IL-2 and other proinflammatory cytokines.

Routes of administration (systemic)

Oral

The preferred corticosteroid is usually prednisone. This may be started at 1 mg/kg and then titrated down as inflammation is controlled and/or steroid sparing agents are added.

Two forms are available: enteric and nonenteric coated. The entericcoated form is associated with fewer upper gastrointestinal side effects but its absorption may be less predictable. It is best given in the morning (coincides with physiological morning cortisol peak).

Intravenous

The preferred corticosteroid is usually methylprednisolone. This may be given as a single 500–1000 mg dose or pulsed, e.g., three doses of 500–1000 mg on consecutive or alternate days given in a 100 mL of normal saline over a minimum of 1 hour.

Efficacy

Box 22.1 Corticosteroids: equivalent anti-inflammatory doses

Contraindications

• Systemic infection (unless covered with appropriate antibiotic(s).

Monitoring

Pretreatment

Given the profound effects of corticosteroids, a short pretreatment review is advised. This includes selected medical history (varicella status, TB status, pre-existing diabetes or impaired glucose tolerance, hypertension) and examination (weight, BP, glucose). If there is any possibility of tuberculosis, a CXR should be performed.

SYSTEMIC CORTICOSTEROIDS: GENERAL 707

During treatment

•BP, weight, glucose every 3 months.

•Lipids every year.

•Bone density (DXA or DEXAscan) if steroid course >3 months; repeated scans may be needed for monitoring bone density in at-risk individuals.

Side effects

Table 22.19 Corticosteroid side effects (selected)

708 CHAPTER 22 Therapeutics

Systemic corticosteroids: prophylaxis

Avoiding side effects

Prophylaxis of corticosteroid-induced osteoporosis

Consider prophylaxis (e.g., a bisphosphonate such as alendronic acid) if treating with the equivalent of 7.5 mg prednisone per day for 3 months in 1) patients >65 years of age, or 2) <65 years of age with previous fragility fracture and/or low DXA scan.

Prophylaxis of gastrointestinal side effects

Consider prophylaxis (e.g., an H2 antagonist such as ranitidine 150 mg 2x/ day) if at risk, i.e., higher doses of corticosteroid, history of gastrointestinal disease, coadministration of NSAIDs (avoid if possible).

Withdrawal of corticosteroids

For most patients with short courses (<10 days) of doses 40 mg/day prednisone (or equivalent), no tapering is necessary. However, when there is a risk of adrenal suppression (Box 22.2), tapering is required in which the dose is reduced fairly rapidly to physiological levels (equivalent to 7.5 mg prednisone/day) and thereafter reduced more gradually. One suggested tapering approach is given in Box 22.3.

Box 22.2 Increased risk of adrenal suppression from corticosteroid administration

•The daily dose has been >40 mg/day prednisone (or equivalent)

•The duration has been >3 weeks

•The frequency has been >1x/day

•There have been other courses recently or long-term steroid administration within the last year.

Box 22.3 Tapering schedule recommended by Consensus Panel on Immunosuppression for Ocular Disease

•Over 40 mg/day: reduce by 10 mg/day every 1–2 weeks

•40–20 mg/day: reduce by 5 mg/day every 1–2 weeks

•20–10 mg/day: reduce by 2.5 mg/day every 1–2 weeks

•10–0 mg/day: reduce by 1–2.5 mg/day every 1–4 weeks

Reprinted with permission from Jabs DA, et al. (2000). Am J Ophthalmol 130:492–513.

OTHER SYSTEMIC IMMUNOSUPPRESSANTS 709

Other systemic immunosuppressants

Indications and mechanism

Although corticosteroids are usually the drug of choice in severe systemic or ocular inflammation, other immunosuppressants have an important role as second-line agents in unresponsive cases or in facilitating reduction and withdrawal of corticosteroids to minimize their side effects.

Table 22.20 Immunosuppressants and their mechanisms

Cautions

These immunosuppressive agents should only be administered by someone with appropriate experience in their use (normally a PCP, rheumatologist, or immunologist) and with adequate monitoring.

Patient education is essential. This will include the potential side effects, necessary precautions (e.g., contraception during and for a period after taking most of these agents), and warning symptoms that would require urgent medical review (e.g., features suggestive of infection, especially sore throat).

Miscellaneous

Eponymous syndromes 712

Web resources for ophthalmologists (1) 718

Web resources for ophthalmologists (2) 719

Reference intervals 720

712 CHAPTER 23 Miscellaneous

Eponymous syndromes

Aarskog’s syndrome X-linked; megalocornea, hypertelorism, antimongoloid palpebral fissures; short stature, syndactyly.

Aicardi’s syndrome probably X-linked lethal to males; corpus callosal agenesis and other CNS abnormalities, infantile spasms, mental retardation, vertebral, and rib malformations; chorioretinal lacunar defects, colobomata.

Alagille’s syndrome Autosomal dominant (Ch20); posterior embryotoxon, optic disc drusen, pale fundi, hypertelorism; intrahepatic bile duct hypoplasia, butterfly vertebrae, congenital heart disease.

Albright syndrome Disorder of G-proteins resulting in polyostotic fibrous dysplasia (of bone), endocrine abnormalities (including precocious puberty), and café-au-lait spots; orbital involvement may cause proptosis, sinus mucoceles, and compressive optic neuropathy.

Alport syndrome Disorder of type IV collagen; X-linked dominant but autosomal inheritance described; anterior lenticonus, anterior polar and cortical cataracts, fleck retina; sensorineural deafness, nephritis.

Alstrom-Olsen syndrome Autosomal recessive; cone-rod dystrophy with features of retinitis pigmentosa, posterior subcapsular cataracts; diabetes mellitus, sensorineural deafness, nephropathy, obesity, acanthosis nigricans.

Anderson–Fabry disease See Fabry’s disease.

Apert syndrome. Autosomal dominant (Ch10); craniosynostosis, syndactyly, broad distal phalanx of great thumb/toe, mental handicap; hypertelorism, proptosis, strabismus, keratoconus, ectopia lentis, congenital glaucoma, optic atrophy.

Arnold–Chiari malformation Congenital herniation of the cerebellum/ brainstem through the foramen magnum may cause hydrocephalus, cerebellar signs (e.g., nystagmus, ataxia) and may be associated with syringomyelia.

Bardet–Biedl and Laurence–Moon syndromes Autosomal recessive overlapping conditions; retinitis pigmentosa with early macular involvement; polydactyly, hypogonadism, obesity, microcephaly, nephropathy, dIQ.

Bassen–Kornzweig (abetalipoproteinaemia) Autosomal recessive deficiency of triglyceride transfer protein; retinitis pigmentosa, cataract; spinocerebellar degeneration, steatorrhoea, acanthosis (of erythrocytes).

Batten’s disease (neuronal ceroid lipofuscinosis). Autosomal recessive metabolic disorder resulting in neurodegeneration. Juvenile form: bull’s eye maculopathy, pigmentary retinopathy, optic atrophy, epilepsy, life expectancy <25 years.

Bloch–Sulzberger syndrome (incontinentia pigmenti) X-linked dominant, lethal to males; abnormal peripheral retinal vasculature, gliosis, tractional retinal detachment; abnormal teeth, cutaneous pigment whorls, and CNS anomalies.

EPONYMOUS SYNDROMES 713

Bourneville disease (tuberous sclerosis) Autosomal dominant (Ch9q TSC1, and Ch16p TSC2) phakomatosis with neurocutaneous features and retinal astrocytomas, p. 644.

Brown syndrome Mechanical restriction syndrome attributed to the superior oblique tendon sheath, p. 590.

Caffrey’s disease Hyperplasia of subperiosteal bone and proptosis.

Cogan’s syndrome Idiopathic, probably autoimmune; interstitial keratitis, sensorineural deafness, tinnitus, vertigo, systemic vasculitis (including lifethreatening aortitis).

Crouzon’s syndrome Autosomal dominant (Ch10); craniosynostosis, maxillary hypoplasia, prognathism, hooked nose; proptosis, strabismus, micro/megalocornea, iris coloboma, cataract, ectopia lentis, glaucoma.

De Morsier’s syndrome Optic nerve hypoplasia; midline brain abnormalities including absent septum pellucidum and corpus callosal hypo/ aplasia.

Down syndrome Trisomy 21; 1 in 650 live births; blepharitis, keratoconus, cataracts; musculoskeletal abnormalities, congenital heart disease, dIQ, p. 638.

Duane syndrome Aberrant co-innervation of LR and MR resulting in horizontal-gaze anomalies, p. 590.

Edwards’ syndrome Trisomy 18; 1 in 8000 live births; microphthalmos, glaucoma, cataracts; failure to thrive, congenital heart disease; life expectancy <1 year, p. 638.

Fabry disease X-linked; A-galactosidase A deficiency results in glycosphingolipid accumulation; vortex keratopathy, cataracts (posterior cortical and granular), conjunctival and retinal telangiectasia; peripheral neuropathy with painful Fabry crises, renal failure, angiokeratoma corporis diffusum, lymphedema.

Foster Kennedy syndrome Ipsilateral optic atrophy due to compressive optic neuropathy with contralateral disc swelling from iICP.

Friedreich’s ataxia Autosomal recessive; triplet repeat expansion (GAA) of noncoding region of the frataxin gene (Ch9); degeneration of spinocerebellar tracts (ataxia, dysarthria, nystagmus), corticospinal tracts (weakness, extensor plantars), posterior columns (proprioception) and peripheral neuropathy (with absent tendon reflexes), pes cavus.

Gardner’s syndrome Variant of familial adenomatous polyposis (autosomal dominant) with bone cysts, hamartomas, and soft tissue tumors; atypical CHRPE, p. 510.

Gaucher disease Autosomal recessive; B-glucosidase deficiency; visceromegaly (type I) or neurodegeneration (type II or III); supranuclear palsy (type IIIb).

Gerstmann’s syndrome Dominant parietal lobe lesion resulting in finger agnosia, right/left confusion, dysgraphia, acalculia; may be associated with failure of ipsilateral pursuit movements.

714 CHAPTER 23 Miscellaneous

Gillespie syndrome Variant of aniridia (PAX-6 mutation) with mental retardation and cerebellar ataxia.

Goldenhar syndrome Accessory auricle, limbal dermoid, hypoplasia of face, vertebral anomaly corneal hyposthesia. Duane’s syndrome iris and upper eyelid coloboma.

Goldmann–Favre disease Autosomal recessive; optically empty vitreous, macular retinoschisis, macular changes, peripheral pigmentary retinopathy.

Gorlin’s syndrome Autosomal dominant (tumor suppressor gene PATCHED; Ch9q); multiple basal cell carcinomas, jaw cysts, skeletal abnormalities, ectopic calcification (e.g., falx cerebri); hypertelorism, prominent supraorbital ridges.

Gradenigo’s syndrome VI nerve palsy and pain in V nerve distribution due to lesion at the apex of the petrous temporal bone; this may be related to chronic middle ear infection.

Gronblad–Strandberg syndrome angioid streaks with pseudoxanthoma elasticum.

Hallermann–Streiff–Francois syndrome micropthalmos, cataract, hypotrichosis, blue sclera; dyscephaly, short stature.

Heerfordt’s syndrome: (uveoparotid fever) presentation of sarcoidosis with fever, parotid enlargement, uveitis.

Hermansky–Pudlak syndrome type II oculocutaneous albinism with platelet dysfunction, pulmonary fibrosis, granulomatous colitis.

Kasabach–Merritt syndrome giant hemangioma with localized intravascular coagulation causing low platelets and fibrinogen.

Kearns–Sayre syndrome Mitochondrial inheritance; CPEO, pigmentary retinopathy (granular pigmentation, peripapillary atrophy), and heart block; usually presents before 20 years.

Laurence–Moon syndrome Grouped with Bardet–Biedl syndrome but no obesity or polydactyly.

Leber’s congenital amaurosis Autosomal recessive; blind from birth, eyepoking (oculodigital sign), hypermetropia, sluggish or paradoxical pupillary reflexes, macular dysplasia but fairly normal fundus appearance.

Leber’s hereditary optic neuropathy Mitochondrial inheritance; rapid sequential visual loss in 20s to 30s due to optic neuropathy, p. 528.

Löfgren syndrome: presentation of sarcoidosis with fever, erythema nodosum, bihilar lymphadenopathy.

Louis–Bar syndrome (ataxia telangectasia) Autosomal recessive (Ch11q, ATM gene); conjunctival telangiectasia, progressive oculomotor apraxia; cerebellar ataxia, dIQ, immunodeficiency.

Lowe syndrome (oculocerebrorenal syndrome). X-linked disorder of amino acid metabolism; congenital cataract, microspherophakia, blue

EPONYMOUS SYNDROMES 715

sclera, anterior segment dysgenesis, glaucoma; dIQ, hypotonia, vitamin D–resistant rickets.

Maffuci’s syndrome Multiple hemangiomas and enchondromas (which may cause limb deformities), with risk of malignant transformation.

Marfan syndrome Autosomal dominant (Ch15, fibrillin); ectopia lentis, retinal detachment, glaucoma, axial myopia; arachnodactyly, long-limbed, aortic dissection, p. 258.

Meckel–Gruber syndrome Autosomal recessive; coloboma; microcephaly, occipital encephalocele, cleft lip/palate, polydactyly, polycystic kidney disease.

Menke’s disease X-linked recessive deficiency of copper transport protein; optic atrophy, retinal dystrophy; wiry hair, ataxia, neurodegeneration.

Mikulicz’s syndrome infiltrative swelling of salivary and lacrimal glands.

Millard–Gubler syndrome lesion of the facial colliculus (dorsal pons) resulting in ipsilateral CN VI and VII palsies, ± contralateral hemiparesis.

Miller–Fisher syndrome Variant of Guillan–Barre syndrome characterized by acute external ophthalmoplegia, ataxia, and areflexia.

Niemann–Pick disease Autosomal recessive; deficiency of sphingomyelinase; type A is infantile onset with visceromegaly, neurodegeneration, and cherry-red spot; type B juvenile onset with visceromegaly, rarely cherryred spot; type C has variable onset, vertical supranuclear gaze palsy, ataxia, and neurodegeneration.

Norrie disease X-linked; retinal dysplasia, retinal detachment, leukocoria, vitreous hemorrhage, cataract, phthisis; dIQ, deafness.

Oguchi disease Autosomal recessive; nonprogressive nyctalopia (CSNB), pseudotapetal reflex which normalizes with dark adaptation (Mizuo phenomenon), p. 458.

Parinaud syndrome Lesion of dorsal midbrain resulting in light-near dissociation, supranuclear upgaze palsy, convergence retraction nystagmus, and failure of convergence and accommodation.

Patau syndrome Trisomy 13; 1 in 14,000 live births; cyclopia, colobomata, retinal dysplasia; microcephaly; life expectancy <3 months, p. 638.

Raymond syndrome Lesion of the corticospinal tract in the ventral pons resulting in VI nerve palsy and contralateral hemiparesis.

Refsum’s disease Autosomal recessive; deficiency of phytanic acid A-hydrolase results in accumulation of phytanic acid; pigmentary retinopathy, optic atrophy; ichthyosis, deafness, cardiomyopathy, ataxia.

Riley–Day syndrome (familial dysautonomia) autosomal recessive; more common in Ashkenazi Jews; tear deficiency keratoconjunctivitis sicca, commonly with ulceration, reduced corneal sensation; sensory neuropathy, autonomic dysfunction/crises.