01OverviewDefinition, clinical context and the essential points that orientate the chapter.
HIV status changes the differential diagnosis and the threshold for examination, but it does not determine every ocular diagnosis. People with well-controlled HIV can develop the same refractive, vascular, inflammatory and surgical eye disorders as anyone else. The immediate questions are what has changed in vision, where the lesion lies, and whether the immune system can contain an infection. Ask about interruptions in antiretroviral therapy without blame, including access, adverse effects, swallowing problems and difficulties attending care.
CMV retinitis damages retinal tissue directly. A central lesion can rapidly threaten useful sight, while peripheral damage may progress before the patient notices difficulty reading. Treatment aims to stop further destruction, protect the fellow eye and other organs, and allow immune recovery; it cannot regenerate retina already lost. UK product information governs the medicine example below. Current US NIH opportunistic-infection guidance is identified as supplementary specialist evidence for CMV assessment and coordinated HIV treatment, rather than being represented as a new UK guideline.
Key points
- CMV becomes a particular concern with severe cellular immunodeficiency, often a CD4 count below 50 cells/µL.
- Peripheral infection may spare central acuity and cause few early symptoms.
- An experienced dilated retinal examination usually establishes the diagnosis; blood PCR cannot replace it.
- Syphilis and other infectious posterior uveitides remain important alternatives in someone with HIV.
- Treat active retinal infection and restore immune function through a jointly planned HIV regimen.
- Valganciclovir induction and maintenance doses differ and require adjustment for renal function.
- New inflammation after starting antiretroviral therapy needs examination for infection, immune recovery and structural complications.
02AetiologyUnderlying causes, associations and risk factors, with why each one matters.
CMV reactivation
Latent cytomegalovirus can reactivate when cellular immunity is severely impaired. Advanced untreated HIV, interrupted treatment or virological failure creates a setting in which infection can reach and destroy retinal tissue.
Other ocular pathogens
Herpes simplex, varicella-zoster, toxoplasma and syphilis can produce posterior ocular inflammation. Clinical appearance, immune status and targeted investigation are needed because their treatments are not interchangeable with CMV therapy.
03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.
- 1Retinal necrosis
Viral injury produces areas of opaque, damaged retina that can extend into functioning tissue. Location matters: a relatively small lesion affecting the macula or optic nerve region can have major consequences for central vision.
- 2Muted inflammation
Severe immune dysfunction can produce surprisingly little vitreous inflammation despite destructive infection. A quiet-looking anterior eye and absence of pain therefore have limited value in excluding a serious posterior process.
- 3Immune recovery inflammation
Restored immune responses can generate intraocular inflammation around previously infected tissue. This may produce macular oedema or membranes, but new symptoms after antiretroviral initiation must also be assessed for active infection.
04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.
Ask separately about floaters, blurred areas, missing peripheral vision and difficulty seeing with each eye. A patient may describe altered visual space rather than general blur. Preserved central acuity should not end the assessment when symptoms suggest peripheral disease.
Establish the latest CD4 count, HIV viral load, treatment history and recent opportunistic infections. An old satisfactory result may not describe current immunity after a prolonged treatment interruption. Newly diagnosed HIV may lack any previous immune measurements.
Record monocular visual acuity, pupils and confrontation fields, then obtain a full dilated retinal examination by an appropriately experienced clinician. Direct ophthalmoscopy with a limited view cannot exclude peripheral retinitis. Both eyes require assessment even when symptoms are unilateral.
Ask about swallowing pain, diarrhoea, neurological symptoms and constitutional illness without assuming each symptom has the same cause. Coordinate emergency medical assessment when the patient is unwell; eye referral and investigation of systemic opportunistic disease can proceed together.
05InvestigationsWhat to request, why it matters and how to interpret it.
Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.
- 01
Dilated retinal examination and photographyFirst step - Why
- Identify lesion distribution and record a baseline for treatment response.
- Interpretation and limitations
- The specialist assesses lesion activity, proximity to critical structures and damage in both eyes. Serial photographs help distinguish advancing infection from stable scars; a single image of the posterior pole may miss peripheral pathology.
- 02
CD4 count and HIV viral load - Why
- Assess immune vulnerability and the response to antiretroviral treatment.
- Interpretation and limitations
- These results guide systemic planning but do not identify the cause of a retinal lesion on their own. Improvement in HIV measures is encouraging without proving that an established ocular lesion has become inactive.
- 03
Targeted ocular fluid testing - Why
- Clarify uncertain infectious diagnoses when the retinal appearance is atypical.
- Interpretation and limitations
- Ophthalmology may arrange aqueous or vitreous PCR for relevant pathogens. Interpret results with examination and sampling limitations; neither a negative ocular assay nor a negative plasma CMV PCR reliably excludes every clinically compatible case.
- 04
Baseline blood count and renal assessment - Why
- Plan antiviral safety monitoring and an appropriate renal-adjusted prescription.
- Interpretation and limitations
- Check haemoglobin, neutrophils, platelets and creatinine before treatment. Use the formulation-specific creatinine-clearance dosing table rather than assuming the full adult dose is suitable because a laboratory eGFR appears only mildly reduced.
- 05
Syphilis testing and directed infection assessment - Why
- Investigate treatable alternatives and associated systemic or sexual-health needs.
- Interpretation and limitations
- BASHH recognises retinal, uveal and optic nerve involvement in syphilis. Interpret serology alongside previous treatment and specialist advice; a positive antibody result requires a clinical explanation rather than automatic attribution of every ocular finding.
06Differential diagnosisRealistic alternatives and the features that help distinguish them.
HIV retinal microvascular disease
Cotton-wool spots can accompany HIV-associated microvascular injury. Their presence does not establish CMV infection, and an apparent benign explanation must not substitute for assessment of suspicious advancing retinal lesions.
Ocular syphilis
Syphilis can affect the uvea, retina or optic nerve, sometimes bilaterally. HIV coinfection can complicate presentation; sexual-health assessment and appropriate serology belong in the differential when ocular findings suggest infection.
Other necrotising retinitis
Herpetic retinal infection and toxoplasmic disease can overlap with CMV clinically. An atypical appearance or uncertain response prompts specialist sampling and revision of the working diagnosis rather than automatic escalation of one antiviral.
07ManagementImmediate care, first-line treatment, alternatives and escalation.
01Suspected infectionGet the retina assessed urgentlyFirst stepNew visual symptoms occur with advanced HIV or other strong concern for infectious retinitis.+
- 1Contact the eye emergency service and HIV clinician with the onset, laterality, acuities and immune history.
- 2Arrange same-day assessment and safe travel; deteriorating vision may make independent driving unsafe.
- 3Obtain useful blood tests in parallel, while avoiding a delay for plasma viral results.
- 4Communicate medicines, allergies, renal disease and pregnancy possibility before the specialist treatment decision.
02Confirmed diseaseCombine ocular control with systemic careOphthalmology has identified CMV retinitis and treatment is being organised.+
- 1Document lesion activity and location, then agree systemic antiviral treatment with infectious-disease and pharmacy support.
- 2Consider specialist intravitreal treatment for immediately threatened central structures; local therapy does not automatically replace systemic protection.
- 3Choose the route according to sight threat, illness severity and reliable gastrointestinal absorption.
- 4Plan initiation or optimisation of antiretroviral therapy jointly; the NIH supplementary guidance supports starting within one to two weeks of anti-CMV treatment rather than prolonged deferral.
03Deterioration or transitionReassess activity before changing treatmentVision changes during treatment, or induction is ending and maintenance is being considered.+
- 1Re-examine both retinas for progressing lesions, detachment, fellow-eye disease and immune recovery inflammation.
- 2Review adherence, absorption, renal-adjusted exposure and possible resistance with the treating specialists.
- 3Make the induction-to-maintenance change explicit in the prescription and patient instructions, including who supplies the next course.
- 4Stop maintenance only with specialist agreement. The supplementary NIH criteria require at least three months of CMV treatment, inactive lesions and a CD4 count at least 100 cells/µL sustained for at least three months on ART; ophthalmic follow-up continues after stopping.
Key medicines and prescribing safety1 treatment · regimens, roles and cautions+
Valcyte 450 mg valganciclovir tablets for adult CMV retinitis
For adults with creatinine clearance at least 60 mL/min, the UK SmPC specifies 900 mg orally twice daily for 21 days for induction, then 900 mg once daily for maintenance. Take with food when possible. Reduce according to the SmPC renal table; tablets are not recommended below 10 mL/min and should not be used for haemodialysis patients.Check blood count, platelets and renal function regularly. Do not initiate with neutrophils below 0.5×10^9/L, platelets below 25×10^9/L or haemoglobin below 80 g/L. Review marrow-toxic and nephrotoxic combinations. Breastfeeding is contraindicated; pregnancy requires explicit benefit-risk assessment. Effective contraception is advised during treatment and for at least 30 days afterwards for women of childbearing potential; men require barrier contraception during treatment and for at least 90 days afterwards unless the partner cannot become pregnant.
08ComplicationsImportant consequences, why they occur and why they matter clinically.
Permanent retinal damage
Control of viral replication may preserve remaining sight without restoring areas already destroyed. Visual prognosis must account for macular involvement, optic nerve involvement and the extent of surviving functional retina.
Retinal detachment
Previously infected retina can become structurally weak and develop breaks or detachment. A new shadow or abrupt visual decline during otherwise successful antiviral treatment requires urgent retinal reassessment.
Treatment and recovery morbidity
Antiviral marrow suppression and renal dosing errors can cause serious systemic harm. Immune recovery inflammation may impair sight despite improving HIV control, requiring coordinated management of infection and inflammation.
09Monitoring and follow-upTreatment response, safety checks and longer-term review.
- Agree the monitoring schedule with the HIV and eye teams. Supplementary NIH guidance specifies full blood counts and renal function twice weekly during ganciclovir or valganciclovir induction and at least weekly during maintenance, with more frequent testing when indicated; assign an action route for abnormal results.
- The supplementary NIH schedule examines both dilated retinas at diagnosis, two weeks after treatment begins and monthly while receiving anti-CMV treatment, with later intervals individualised after immune recovery. Record lesion activity and fellow-eye findings; symptom improvement alone cannot justify reducing therapy.
- Give a direct route for new shadows, increasing floaters or sudden blur, including symptoms arising between routine appointments.
- Review antiretroviral access, tolerance and virological response while supporting attendance at eye visits and medication collection.
- After maintenance is stopped, continue the specialist eye follow-up plan because relapse and structural complications remain possible.
10Special situationsVariants, exceptions and circumstances that change the usual approach.
Blood infection and organ disease
A circulating CMV result and a retinal diagnosis answer different questions. Blood positivity can occur without ocular disease, while a negative result can coexist with organ involvement. The urgent decision is whether the visual presentation requires examination, not whether one blood assay is reassuring.
Recovery is not a single diagnosis
New symptoms after antiretroviral initiation can reflect active infection, immune recovery inflammation or an unrelated eye disorder. Do not label the presentation immune reconstitution inflammatory syndrome simply because treatment was recently started, and do not add empirical corticosteroids to undiagnosed retinitis.
A safe handover specifies the phase
An instruction to continue valganciclovir without stating induction or maintenance invites a twofold daily dosing error in someone with normal renal function. Include current renal dosing, the review date and supply responsibility, especially when discharge coincides with a change in treatment phase.
Support without stigma
Explain the purpose of urgent examination and ask permission before involving relatives in medication or travel support. Visual disability, complex treatment and fear of disclosure can each obstruct attendance. A confidential and accessible plan is part of preserving sight.
11Common pitfallsFrequent interpretation and management errors.
- 01
Excluding opportunistic retinal disease because the eye is painless, externally white or still reads small letters.
- 02
Using a negative plasma CMV PCR as the reason to cancel an urgent retinal examination.
- 03
Assuming every retinal abnormality in a person with HIV has a CMV aetiology.
- 04
Continuing the induction dose indefinitely because the discharge letter does not name a transition point.
- 05
Treating new post-ART floaters with corticosteroids before reassessing for active retinal infection.