L'occhio e le malattie sistemiche

Il ruolo dell'occhio nella diagnosi delle malattie sistemiche

An ocular manifestation of a systemic disease or congenital condition may be its first visible presentation. The eye is the only organ in which vascular disease can be observed in vivo. This may enable a clinician to observe signs of systemic disease. Awareness of these associations assists early diagnosis and may help to reduce the risk of complications.

Questo articolo prende prima in considerazione le condizioni che possono influenzare l'occhio, poi esamina le condizioni dell'occhio che possono essere associate a particolari patologie.

For details on how to assess the structure and function of the eye, see the separate Esame dell'occhio article. Where findings do not fit with those expected or are difficult to elicit, referral should be considered.

Parte 1: condizioni che possono influenzare l'occhio

Condizioni endocrine/metaboliche

Diabete mellito¹

Diabetes affects small blood vessels and can be particularly destructive in the eye leading to diabetic retinopathy. This is caused by small vessel blockage causing blood supply, leading to poor delivery of oxygen. Raised blood glucose also acts directly to damage tissue. ²³

The end result is hypoxic damage to the tissues of the eye, particularly the retina, which may become oedematous or grow new compensatory blood vessels which bleed easily. Severe sight impairment can result. Diabetic retinopathy accounts for 80% of visual loss in patients with diabetes.³

77.3% of people with type 1 diabetes and 25.1% of those with type 2 diabetes have diabetic retinopathy on examination.⁴

Examination findings in diabetic eye disease includere:

• Macchie di tessuto cotonoso (aree di ischemia retinica con edema).

• Esudati duri (depositi di grasso).

• Microaneurismi (che appaiono come piccoli punti rossi sulla retina).

• Piccole emorragie di fiamma dalle pareti dei vasi sanguigni danneggiati.

• Segni di formazione di nuovi vasi sanguigni sul retro dell'occhio.

• Diabetes is also a cause of early cataracts, due to excess glucose interfering with the metabolism of the crystalline lens.

The blood vessels on the diabetic fundus may reveal the health of microvasculature elsewhere in the body - as the eyes develop diabetic retinopathy, renal impairment and diabetic neuropathy often develop in a similar timeframe. For greater detail on diabetic eye disease, see the separate Retinopatia diabetica e problemi agli occhi diabetici articolo.

Ipertensione⁵

Vascular changes from hypertension can be seen in vivo in the eye. The changes result from hypertension-induced atherosclerosis affecting the blood vessels, as well as fibrinoid necrosis of the choroidal arterioles.

Hypertensive retinopathy can be characterised as mild, moderate or severe.

• In mild disease there is narrowing of the vessels, referred to as 'silver wiring' because of the characteristic appearance. The arteries then swell and compress the veins where they cross over, causing "arteriovenous nicking".

• Moderate disease causes haemorrhages, micro-aneurysms, cotton wool spots (caused by micro-infarcts from obstructed blood vessels) and hard exudates (lipid deposits).

• Severe disease is demonstrated by the development of papilledema, due to an increase in intracranial pressure. A macular star refers to the radial streaks of exudates that arise around the macula in severe hypertensive retinopathy.

Malignant hypertension definitions differ but the 2020 international hypertension societies define it as a severe elevation of blood pressure, typically above 200/120 mm Hg, accompanied by advanced bilateral retinopathy characterized by retinal haemorrhages, cotton wool spots, and papilledema.⁶

Retinopathy often stabilises with treatment of hypertension; however, arteriole narrowing and vessel crossing changes often remain. ⁶Visual loss is rare but complications of hypertensive retinopathy can include optic neuropathy and central vein or artery occlusions, particularly if left untreated. Malignant hypertension retinopathy with papilloedema has a strong correlation with increased cardiovascular morbidity and mortality.⁷

Ipertiroidismo

malattia di Graves may cause proptosis due to an inflammatory orbital process and remodelling of surrounding connective tissue. This may be the first sign of the condition and may be unilateral or bilateral. Le complicazioni oculari della malattia orbitale tiroidea include corneal ulceration and visual loss.⁸

Iperlipidemia

Corneal arcus may be present at birth, but usually appears in patients aged over 50; it results from cholesterol deposits and can be associated with iperlipidemia.

Acromegalia

Atrofia ottica is common. There may be nistagmo.

sindrome di Cushing

Iatrogeno sindrome di Cushing may be associated with steroid-induced cataracts (this is not the case for Cushing's disease) and susceptible individuals may also develop glaucoma. Occasionally, a secreting pituitary tumour can cause bitemporal hemianopia.

Condizioni infiammatorie e autoimmuni ⁹¹⁰

Disturbi del tessuto connettivo

Those disorders which particularly affect joints can also inflame the eye, causing scleritis or uveitis. They are also often associated with dry eyes due to dysfunction of the lacrimal and meibomian glands. These include:

• Artrite reumatoide (often with episcleritis, scleritis and dry eyes).

• Lupus eritematoso sistemico (keratoconjunctivitis sicca, ulcerative keratitis, and (rarely) scleritis, retinal vasculitis, or optic neuropathy).

• Malattia di Behçet (usually oral ulceration is the predominant feature).

• Ankylosing spondylitis (AS). Fino al 25% dei pazienti con AS sviluppa irite in qualche momento.

• Artrite reattiva - (conjunctivitis and uveitis).

• morbo di Crohn.

• Colite ulcerosa.

• Sarcoidosi (conjunctival granulomas and posterior uveitis). Less commonly, there may be fundal granulomas, neovascularisation and papilloedema.

• Sindrome di Sjögren (most commonly as keratoconjunctivitis sicca and occasionally as episcleritis or scleritis).

• Sclerosi sistemica: il rassodamento delle palpebre e le telangiectasie sono comuni.

• The inflammation of small arteries in giant cell arteritis may cause sudden unilateral transient or permanent visual loss.

• Poliarterite nodosa: cheratite ulcerativa e sclerite sono comuni. I pazienti possono anche sviluppare un pseudotumore orbitale e una periarterite retinica ostruttiva.

• Artrite psoriasica: questo può essere associato a uveite, congiuntivite, cheratite o cheratocongiuntivite secca.

• Dermatomiosite: provoca colorazione viola e edema delle palpebre con edema della congiuntiva.

• Sindrome di Stevens-Johnson: la congiuntivite è comune. Potrebbero anche esserci lieve uveite anteriore, cheratopatia puntata superficiale e (raramente) panopthalmitis.

Acute anterior uveitis is a particular feature in AS, Crohn's disease, ulcerative colitis, juvenile idiopathic arthritis, and sarcoidosis. In AS, it may occur in up to 30% of patients. In Crohn's disease and ulcerative colitis, it may be accompanied by conjunctivitis, episcleritis, and (rarely) retinal complications (periphlebitis).

Sclerosi multipla

The optic nerve may be the first to be affected by the acute demyelination of sclerosi multipla (SM) resulting in neurite ottica.¹¹

• Around 18% of optic neuritis patients presenting with no systemic abnormalities and a normal MRI will go on to be diagnosed with MS in the first year.¹²

• Circa il 50% dei pazienti che presentano un primo episodio di neurite ottica ma nessun altro segno di SM hanno lesioni demielinizzanti alla risonanza magnetica.

Miastenia grave

Miastenia grave often presents as ptosis. The picture is of fluctuating, asymmetric external ophthalmoplegia with ptosis and weak eye closure. Patients often have an inability to maintain upward gaze.

Pemfigo cicatriziale¹³

Most patients have cicatrising conjunctivitis where bullae are progressively replaced by conjunctival ulceration, shrinkage, and scarring. These patients may also complain of dry eye and of adhesions within the conjunctiva and between the upper and lower lids.

Condizioni infettive

Ocular presentation can be associated with a number of chronic infections including tubercolosi, sifilide e toxoplasmosi.

Toxoplasmosi

This can cause retinochoroiditis. Up to 85% of children born with congenital toxoplasmosis eventually develop ocular involvement, even when the infection is subclinical at birth. The prevalence of ocular toxoplasmosis in people who contract toxoplasmosis postnatally varies with geographical location, having been found to be between 2 and 18%.¹⁴

Infezioni fungine dell'occhio

These may lead to severe inflammation, with cotton wool 'fluff' in the back of the eye and visual loss. They occur in more than a million people worldwide each year and are increasing in incidence. This is thought to be due to the increasing number of patients with risk factors such as immunosuppression, use of medical devices, widespread use of antimicrobials, and, at the time of the study, hospitalised patients with COVID-19.¹⁵ They are more common in LEDCs than MEDCs.¹⁶

HIV/AIDS¹⁷

There are many ophthalmic features associated with AIDS. The ocular problems can be summarised as follows:

• External disease: Sarcoma di Kaposi (eyelids and conjunctiva), multiple molluscum lesions, severe herpes zoster oculare, carcinoma a cellule squamose.

• Cornea: virus dell'herpes, microsporidial keratoconjunctivitis, bacterial and fungal keratitis, cheratite da citomegalovirus.

• Varie forme di uveite, generalmente gravi.

• Retinitis, HIV retinopathy, choroiditis, linfoma intraoculare a cellule B.

• Neuro-ophthalmological problems - for example, cranial nerve palsies, pupillary abnormalities, squints, visual field defects, and visual hallucinations.

Malattia da graffio di gatto

Occasionally, malattia da graffio di gatto neuroretinitis can occur and, more rarely, other ocular features - for example, uveitis, retinitis, and retinal detachment.

Leprosy (Hansen's Disease)

Ocular involvement in HD is estimated at 70–75% worldwide. About 10–50% suffer from severe ocular symptoms and loss of vision occurs in approximately 5% of cases. Ocular changes may persist or worsen even after patients are considered cured.¹⁸

malattia di Lyme

Up to a half of those with confirmed Lyme disease have been shown to have ocular manifestations, most commonly diplopia and strabismus, but also anterior segment findings, including conjunctivitis, keratitis, and cataracts, (23.76%), posterior segment findings, which included retinitis, chorioretinitis, neuroretinitis, posterior uveitis, intermediate uveitis, and retinal vasculitis, (19.66%), third cranial nerve palsy (18.65%), and optic nerve findings (10.76%).¹⁹

Sifilide

Acquisita sifilide commonly results in keratitis. Less commonly, there is uveitis, chorioretinitis and neuroretinitis. Babies with congenital syphilis tend to have uveitis and keratitis; later on there is a pigmentary retinopathy.

Other infectious causes²⁰

Infections which are more common worldwide but very rare in the UK can cause ocular manifestations. These include:

• Avian influenza virus - conjunctivitis

• Zika virus - anterior uveitis, retrobulbar pain, congenital Zika disease (visual impairment)

• Ebola virus - uveitis, optic neuropathy

• Nipah virus - diplopia, photophobia, Horner syndrome, abnormal Doll's eye, retinal artery occlusion

• Dengue virus - uveitis, retrobulbar pain, optic neuropathy, photophobia, conjunctival injection

• Chikungunya virus - uveitis, sub-conjunctival haemorrhage, maculopathy, vasculitis, optic neuropathy, endophthalmitis, photophobia, conjunctival injection

Condizioni congenite

Albinismo²¹

Ocular symptoms in albinism are the most significant clinical feature. They include photophobia, refractive errors, foveal hypoplasia, horizontal nystagmus, strabismus and reduced stereopsis.

Sindrome di Down²²

Ocular features include Brushfield's spots (small white spots on the periphery of the iris). Children with Sindrome di Down commonly have epicanthal folds at the inner corners of the eyes.

They are more likely to have strabismus, amblyopia, accommodation defects, refractive errors, nasolacrimal duct obstruction, nystagmus, keratoconus, congenital cataracts, and retinal and optic nerve abnormalities.

Sindrome di Ehlers-Danlos (tipo 6)

The eyes of patients with Sindrome di Ehlers-Danlos (tipo 6) are particularly susceptible to trauma. They frequently have blue sclerae and a microcornea. A misplaced lens, keratoconus, high myopia, and retinal detachment are also seen.

Sindrome di Marfan

Lens dislocation, myopia, retinal detachment, and anomalies with the iridocorneal angle and pupil function are common in Sindrome di Marfan.

Distrofia miotonica

Spesso si riscontrano cataratte precoci e ptosi; possono esserci anche anomalie nei movimenti oculari e nella funzione pupillare.

Neurofibromatosis-1

In neurofibromatosis-1 there may be eyelid neurofibromas as well as nodules on the iris. Optic nerve neuroma can cause unilateral sight loss. Proptosis can occur and there may be abnormalities of colour vision. Occasionally, there are other tumours.

Neurofibromatosi-2

Patients with neurofibromatosis-2 develop early cataracts; some also develop ophthalmoplegia and intraocular hamartomas.

Retinite pigmentosa

In retinite pigmentosa, si osserva una pigmentazione anomala nell'occhio.

Sclerosi tuberosa

Retinal astrocytomas occur in 50% of patients with sclerosi tuberosa. Meno comunemente, si sviluppano macchie ipopigmentate sull'iride e sulla retina; l'aumento della pressione intracranica può causare papilloedema e paralisi del sesto nervo.

Cancro

Cancer can arise in or metastasise to the eye. The most common primary eye tumour is a melanoma coroideale. See the separate articles Tumori del nervo ottico e dell'occhio, Tumori retinici e Retinoblastoma.

Condizioni ematologiche

Anemia

Emorragia, macchie di cotone, emorragia subcongiuntivale e, se la vitamina B12 è bassa, può verificarsi neuropatia ottica. La gravità è correlata alla severità dell'anemia.

Emoglobinopatie

La malattia falciforme e le talassemie possono causare malattie oculari. I problemi includono occlusioni vascolari, anastomosi e proliferazione, emorragia vitreale e distacco della retina.

Stati di iperviscosità

Questi possono causare emorragie, aree di coton fiocco e alterazioni delle vene retiniche. La policitemia e il mieloma multiplo possono causare gonfiore del disco ottico così come cisti nell'iride e nel corpo ciliare. Possono anche verificarsi cristalli corneali.

Leucemia

Risultati simili all'anemia così come cambiamenti pigmentari nella retina ('macchie di leopardo') e emorragie spontanee. L'infiltrazione provoca una varietà di sintomi a seconda della zona in cui si verifica.

Anemia falciforme

Anemia falciforme causes abnormal retinal vessel formation which may lead to bleeding into the retina.

Condizioni della pelle

Rosacea

Many patients with rosacea have chronic blepharitis and recurrent meibomian cysts. Occasionally there is also severe conjunctivitis and keratitis.

Condizioni meno comuni che colpiscono l'occhio

Heterochromia

In this condition, one iris is a different colour from the other. It may be genetically inherited or acquired by disease or injury. It is associated with Waardenburg's syndrome (with deafness and a white streak of hair) and with Malattia di Hirschsprung.

Sindrome di Kearns-Sayre

A rare mitochondrial myopathy characterised by chronic progressive external ophthalmoplegia, cardiac conduction abnormalities, and pigmentary retinopathy.

Ipertensione intracranica idiopatica

Ophthalmic features may include frequent transient visual obscurations (up to 30 a day) diplopia, visual field defects, and disc swelling which is usually bilateral.

Paralisi sopranucleare progressiva

Progressive ophthalmoplegia in paralisi sopranucleare progressiva is associated with dementia and truncal stiffness.

sindrome di Sturge-Weber

Patients with sindrome di Sturge-Weber frequently have ipsilateral glaucoma and a diffuse choroidal haemangioma. Occasionally, there is an ipsilateral episcleral haemangioma.

Sindrome di Vogt-Koyanagi-Harada (VKH)

Nella sindrome di VKH si osserva uveite anteriore, insieme a cambiamenti cutanei. La malattia di Harada, inoltre, presenta caratteristiche neurologiche e predomina il distacco della retina.

Malattia di Von Hippel-Lindau (VHL)

In malattia di VHL there may be capillary haemangiomas of the retina or the optic nerve head. Vessel leakage can cause visual deterioration

Granulomatosi con poliangite (GPA)

Ophthalmic features of GPA include nasolacrimal duct obstruction and dacrocystitis. Patients with the condition may also develop scleritis, peripheral ulcerative keratitis (± peripheral corneal thinning), and orbital pseudotumour.

Parte 2: condizioni degli occhi e le loro associazioni

Questa sezione esamina le malattie sistemiche che colpiscono l'occhio da una prospettiva opposta, analizzando le caratteristiche di presentazione e elencando le condizioni con cui possono essere associate.

Cataratta²³

Most cataratta are age-related but they are also associated with underlying conditions. They are more common in diabetes and Down's syndrome. They may be associated with steroid use, certain rare hormone deficiencies, previous eye trauma, congenital rubella, and many rare congenital conditions. The list below offers examples but is not exhaustive.

• Anomalie metaboliche:

  • Diabete mal controllato.

  • Deficit di fosfofruttochinasi.

  • deficit di G6PD.

  • Ipouricemia associata a disidratazione e malattia renale cronica.

• Altre malattie sistemiche:

  • Distrofia muscolare.

  • Dermatite atopica.

  • Neurofibromatosi-2.

  • Congenital rubella.

  • Sindrome di Lowe.

  • Malattia di Refsum.

  • Ipoparatiroidismo.

• Esposizione ai farmaci:

  • Steroidici (incluso l'uso prolungato di corticosteroidi topici).

  • Clorpromazina.

  • Busulfano.

  • Amiodarone.

  • Oro.

  • Allopurinolo.

Uveite

Although many cases of uveite are idiopathic, there are well recognised associations with systemic disease, particularly in atypical presentations, repeat presentations and immunocompromised patients.

Uveitis might be expected in any disease process which has the capacity to affect joints, given that the eye is a modified joint. Examples include inflammatory disorders such as artrite reumatoide, SA), infections (for example, tubercolosi, candidosi) and with infestations (for example, toxoplasmosi, toxocariasi).

Acute anterior uveitis is associated with HLA-B27.²⁴

occlusione della vena centrale della retina²⁵

Ostruzione della vena centrale della retina (CRVO) is associated with ipertensione, diabete, smoking, iperlipidemia, hyperviscosity states (particularly in patients aged less than 45 years), glaucoma, trombofilia, and vasculite.

There may be an underlying haematological problem (for example, fattore V Leiden, mieloma, o sindrome da anticorpi antifosfolipidi) or systemic inflammation (for example, rheumatoid arthritis, AS).

Ostruzione dell'arteria retinica centrale ²⁶

Ostruzione dell'arteria retinica centrale (CRAO) is an ophthalmic emergency. It may be caused by atherosclerosis, emboli or inflammatory causes (for example, giant cell arteritis, GPA, systemic lupus erythematosis, and polyarteritis nodosa, among others).²⁷

Haematological causes include protein S deficiency, carenza di proteina C and antithrombin deficiency as well as antiphospholipid syndrome, leukaemia and lymphoma. CRAO also been known to occur in emicrania.

Amaurosi fugace

Amaurosis fugax is due to transient ischaemia and may be a feature of embolic, thrombotic, vasospastic, or haematological problems. These include attacchi ischemici transitori, giant cell arteritis, Takayasu's arteritis, e anemia falciforme. It is also seen in stenosi dell'arteria carotide.

Anomalie pupillari

Pupillary abnormalities are found in a number of conditions. sindrome di Horner results from unilateral interruption of the sympathetic system on one side of the face, causing ptosis, miosis, and lack of sweating on that side of the face. The path of the sympathetic fibres is so tortuous that it is a poor localising sign but it is a very good lateralising sign.

Movimenti anomali degli occhi

Abnormal eye movements and squints are found in many conditions affecting the cranial nerves or their corresponding brainstem nuclei. These include cerebrovascular accidents, aneurysms, and diabetes.

Transient paralysis of cranial nerves III, IV or VI may occur during emicranie oftalmoplegiche with full recovery.

La Dott.ssa Mary Lowth è un'autrice o l'autrice originale di questo opuscolo.