Yellow White Retinal Lesion Differential Diagnosis

Yellow-white retinal lesions or deposits at the macula are caused by a wide range of conditions and can lead to vision loss.

Causes of Yellow White Retinal Lesion:

  1. Drusen and drusen-like conditions
  2. Hard exudates
  3. Cotton wool spots
  4. Retinal Infiltrate
  5. Choroidal neovascularization
  6. Chorioretinal scar
  7. Crystalline maculopathies
  8. Flecked retinal syndromes 
Yellow White Retinal Lesion Differential Diagnosis
Yellow White Retinal Lesion Differential Diagnosis

1- Drusens:

are tiny yellow or white accumulations of extracellular material that build up between Bruch’s membrane and the retinal pigment epithelium of the eye.They are rarely seen before the age of 45 years, and increase between the ages of 45 and 60 by which time they are almost universal. There are five main types, with hard and soft drusen being the commonest.

Types of drusens:

Hard drusen : are small and discrete. These patients are at increased risk of subsequent visual loss from geographical atrophy
Soft drusen: these are larger and paler than hard drusen and are associated with an increased risk of exudative age-related macular degeneration (AMD)
Basal laminar drusen : a myriad of small, round, uniformly sized, slightly raised yellow subretinal lesions. Fluorescein angiography enhances their appearance so that hundreds of bright spots appear, giving a ‘starry-sky’ appearance. They occur in middle-aged individuals who are usually asymptomatic until they develop pseudovitelliform lesions, the accumulation of yellow material at the fovea that can simulate a choroidal neovascular membrane. This resolves without a scar, producing less visual loss than a true subfoveal choroidal neovascular membrane (CNV).
Calcified drusen : drusen may acquire a glistening appearance due to calcification which can occur in any type of drusen. These are often seen adjacent to areas of RPE atrophy.
Drusenoid RPE detachment : caused by coalescence of large areas of soft drusen, this is a precursor of AMD. 

Fluorescein Angiography of Drusen:

The majority of patients with AMD have drusen and RPE abnormalities with no significant visual loss.

FA is not usually indicated in these cases unless we suspect the presence of choroidal neovascularization (CNV).

Several types of drusen can be identified. Hard drusen are small (<63 µm), round, well-defined, yellowish deposits that correspond to accumulation of hyaline material in the inner and outer collagenous zones of Bruch’s membrane.

On FA, they appear hyperfluorescent as transmission defects due to overlying RPE thinning.

On occasion there may be a myriad of small drusen, termed cuticular or basal laminar drusen, which appear as a “starry sky” on FA .

Soft drusen are larger (>63 µm) with poorly defined borders and they tend to coalesce and become confluent.

Their angiographic appearance depends on the thinning of the overlying RPE, the histochemical composition and the age of the patient.

They are hyperfluorescent with phospholipid accumulation and in younger patients.

Soft drusen represent localized detachments of the RPE.

It is very usual to find both hard and soft drusen in the same eye of a patient.

The confluence of soft drusen can produce a drusenoid pigment epithelial detachment (PED), which shows hyperfluorescence and dye pooling without leakage beyond its margin with typical areas of focal hyperpigmentation .

In addition to drusen we can find RPE abnormalities, namely hyperpigmentation.

Focal hyperpigmentation is a risk factor for the development of choroidal neovascularization (CNV) and angiographically appears as a blocked fluorescence

Histopathologically it is characterized by focal RPE hypertrophy and pigment migration into the subretinal space.

It also displays focal hyperautofluorescence suggesting that these cells contain lipofuscin


2- Hard Exudates:

Hard exudates are lipid deposits that are produced by lipoprotein leakage from blood vessels. The novice is often
concerned about how to distinguish them from drusen but careful biomicroscopy will show that hard exudates are
located more anteriorly in the retina than drusen, occurring between the inner plexiform and inner nuclear layers. They have a yellow waxy appearance with well-defined margins. They may take on a number of patterns, such as circinate (ring), clumps, or stellate configuration, depending on the underlying cause, whereas drusen tend to be
more randomly spread. Signs of underlying conditions that may cause leakage and formation of hard exudates may
be present, such as microaneurysms in diabetic retinopathy, or vessel dilatations in Coats’ disease.

Hard Exudates
Hard Exudates

Circinate or clump pattern of hard exudates :

These are the result of chronic leakage from capillaries in the macula. Common causes are diabetic maculopathy, branch retinal vein occlusion, and retinal artery macroaneurysm. Other rarer causes include radiation retinopathy,and retinal telangiectasia. The cause may be obvious, with multiple microaneuryms in diabetic retinopathy, and the sectoral distribution of a branch vein occlusion.

Stellate maculopathy:

This occurs when hard exudates form a star pattern at the macula which may be complete or incomplete . Bilateral features with disc swelling may be caused by severe hypertension or papilloedema and require emergency referral.Neuroretinitis (inflammation of the optic nerve and retina from various causes) and capillary angioma (on the disc or in the periphery) are rarer causes .

Subretinal exudates:

These are exudates deep to the retina that are associated with serous elevation of the overlying retina. These tend
to be distinct from the other forms producing a large exudate rather than a pattern of small exudates. They may
be seen with chronic leakage from a choroidal neovascular membrane, Coats’ disease and Toxocara canis. Coats’ disease typically occurs in children and is characterised by telangiectatic and aneurysmal retinal vessel changes. These lead to intra- and subretinal exudates that progress to massive subretinal exudate and exudative detachment. This can present as leukocoria.

Fluorescein Angiography of Hard Exudate:

 On angiography, small dots are not visible, but larger patches may block choroidal fluorescence and may be masked by leakage from microaneurysms that is hyperfluorescent.  Exudates are differentiated from drusen which hyperfluoresce during the transit phase and become less prominent in late phases.


3- Cotton wool spots :

A fluffy white patches on the retina. They are caused by damage to nerve fibers and are a result of accumulations of axoplasmic material within the nerve fiber layer. There is reduced axonal transport (and hence backlog and accumulation of intracellular products) within the nerves because of the ischemia. This then causes the nerve fibers to be damaged by swelling in the surface layer of the retina.

Cotton woll spots Causes:

– Ischemic : hypertension, diabetes, ocular ischemic syndrome, retinal vein occlusion, anemia, hyperviscosity state, hypercoagulable state, radiation, acute blood loss.

– Immune and inflammatory conditions: systemic lupus erythematosus, dermatomyositis, scleroderma, polyarteritis nodosa, giant cell arteritis.

– Infectious: HIV retinopathy, cat-scratch disease, rocky mountain spotted fever, leptospirosis, onchocerciasis, bacteremia, fungemia.

– Embolic: carotid emboli, cardiac emboli, cardiac valvular disease, endocarditis, rheumatic heart disease, deep venous emboli, Purtscher-like retinopathy, foreign-body emboli.

– Neoplastic: lymphoma, leukemia, metastasis.

– Medication induced: interferon retinopathy.

– Miscellaneous: trauma, epiretinal membrane, high-altitude retinopathy, papilledema, papillitis, Purtscher retinopathy.

– Idiopathic.

Cotton woll spots FFA:

In the mid-phase fluorescein angiogram of the cotton-wool spots are hypofluorescent. Late-phase angiogram demonstrates staining of the cotton-wool spots, numerous microaneurysms, and capillary leakage.


4- Retinal Infiltrates :

Yellow-white area with fuzzy edges. It consists of inflammatory cells, dead retinal tissue, and perhaps micro-organisms. Its indistinct margins and overlying vitreous haze distinguish it from other yellow-white things in the retina.

Causes of retinal infiltrates:

Toxoplasmosis,Behcet’s Disease,systemic bacterial sepsis, candidiasis, herpes simplex or zoster, sarcoid, lues, lymphoma, leukemia, metastasis and filariasis.

Fluorescein Angiography of retinal infiltrates:

Differs according to its site (superficial infiltrates leads to blockage of fluorescein – deep sub RPE infiltrates may cause hyperfluorescence.


5- Choroidal neovascularization:

Choroidal neovascularization (CNV) involves the growth of new blood vessels that originate from the choroid through a break in the Bruch membrane into the sub–retinal pigment epithelium (sub-RPE) or subretinal space. CNV is a major cause of visual loss.

It appears as gray green or pinkish yellow lesion and may be associated with:

  • Subretinal blood
  • Subretinal fluid
  • Lipid exudation
  • Retinal pigment epithelial detachment
  • Subretinal fibrosis (disciform scar)

Causes Of of choroidal neovascularization ( CNV ):

Degenerative : Age related macular degeneration,pathological myopia,optic disc drusen and angiod streaks.

Inflmmatory Diseases: POHS ( presumed ocular histoplasmosis syndrome ) and posterior uveitis ( toxoplasmosis and Vogt Koyanagi Harada syndrome ).

Trauma : Choroidal rupture and laser photocoagulation.

Tumours: Choroidal nevus and choroidal hemangioma.

Fluorescein Angiography of classic choroidal neovascularization ( CNV ):

FA is an essential tool in diagnosing and managing CNV. Angiographic patterns that have been described for CNV include the following:

  • A lesion that hyperfluoresces in the early phases of the angiogram, maintains well-demarcated borders, and leaks late (obscuring its borders) – Classic CNV
  • A lesion whose borders cannot be determined by FA – Occult CNV
  • A lesion, well demarcated or poorly demarcated, that is elevated solidly and hyperfluoresces irregularly to different degrees – Fibrovascular pigment epithelial detachment (PED); a form of occult CNV
  • A lesion that demonstrates irregular, indistinct, late, sub-RPE leakage – Late leakage of undetermined source (LLUS); a form of occult CNV

According to its location relative to the center of the fovea, CNV has been classified as follows:

  • Extrafoveal (200-1500 µm)
  • Juxtafoveal (1-199 µm)
  • Subfoveal

OCT of classic choroidal neovascularization ( CNV ):

  • OCT plays a major role in the management of CNV specially occult CNV ; despite its many advantages, however, OCT cannot replace FA in the management of CNV
  • Well-defined CNV is seen as a fusiform thickening of the RPE-choriocapillaris band
  • Poorly-defined CNV is seen as a diffuse area of choroidal hyperreflectivity that blends into the normal contour of the normal RPE band
  • A normal boundary cannot be defined
  • A subretinal hemorrhage is seen as a layer of moderate reflectivity that elevates the neurosensory retina and causes optical shadowing, resulting in a lower reflectivity of the underlying RPE and choroid
  • A serous RPE detachment is characterized by complete shadowing of the underlying structures
  • A hemorrhagic RPE detachment shows a moderately reflective layer beneath the detached RPE
  • A fibrovascular RPE detachment demonstrates moderate reflectivity throughout the entire sub-RPE space under the elevation
  • Detachments of the neurosensory retina appear as elevations of a moderately reflective band above the RPE band
  • RPE tears can be seen as thick elevated areas of high reflectivity; the underlying choroid is completely shadowed, whereas the adjacent choroid reveals a hyperreflective image because of the absence of RPE
  • Retinal edema or thickness can be measured objectively by defining the anterior and posterior borders of the retina


CNV vs Chorioretinal scar
CNV vs Chorioretinal scar

6- Chorioretinal scar : 

A chorioretinal scar is an area of pigmentary change or fibrosis that is located on the inside surface of the eye. These may be the result of an old infection ( toxoplasmosis scar ) or injury, but in some cases we do not know the source. If the chorioretinal scar is in the central retina, it can cause decreased vision. However, in most cases it is located away from the center and does not cause any problems.

Fluorescein Angiography of chorioretinal scar:

Fluorescein Staining :late hyperfluorescence resulting from the accumulation of fluorescein dye into certain tissues. 


7- Crystalline maculopathies :

Multiple yellow crystalline deposits at the macula can be caused by drugs, and much more rarely by hereditary or
metabolic disorders. Tamoxifen, a specific anti-oestrogen used in the treatment of breast cancer, can cause retinotoxicity at high doses and more rarely after long-term use at low doses. Bilateral multiple superficial ,  crystalline deposits are seen at the macula with retinal toxicity consisting of decreased visual acuity and colour vision.Discontinuation of treatment prevents further progression but there may not be full recovery of visual function.Other drugs that can induce a crystalline maculopathy include canthaxanthin, an oral tanning agent, and talc, associated with cocaine and heroin use. All patients with crystalline maculopathy require referral for diagnosis and management.

8- Flecked retinal syndromes:

There are a group of rare predominantly recessively inherited disorders characterised by yellow flecks deep in the retina.
● Fundus flavimaculatus : This occurs in adults, and is characterised by ill-defined, yellowish flecks that are often of a fishtail or crescentic shape. They are present deep in the retina, below the level of the retinal vessels, and are symmetrically distributed . The visual prognosis is good unless there is macular involvement.
● Stargardt’s disease : This presents in childhood with a similar appearance to fundus flavimaculatus. However, there is early foveal involvement with an oval lesion that has a ‘beaten-bronze’ appearance and leads to atrophy with loss of vision .
● Fundus albipunctatus : (a form of congenital stationary night blindness) also features multiple yellow spots deep in the retina, which tend to spare the macula. These flecks need to be distinguished from drusen, but the shape, depth and symmetrical distribution of the lesions should aid this. Drusen are more sharply delineated, rounder, and whiter. All these patients should be referred for diagnosis and genetic counselling.



1 Kanski JJ, Nischal KK, Milewski SA. Ophthalmology: Clinical Signs and differential Diagnosis, Philadelphia: Mosby, 1999.

2 Kanski JJ. Clinical Ophthalmology: A Systematic Approach, 6th ed, Edinburgh: Butterworth-Heinemann Elsevier, 2007.

3 Ryan SJ. Retina. 4th ed, Philadelphia, Pa: Elsevier/Mosby, 2006.

4 Nussenblatt RB, Whitcup SM. Uveitis: Fundamentals and clinical practice, 3rd ed, Philadelphia: Mosby 2004.

5 Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S, for the ANCHOR Study Group. Ranibizumab versus Verteporfin for Neovascular Age-Related Macular Degeneratio. NEJM

7-Retina Videos

8-Retinal Diseases Signs In One Picture

Yellow White Retinal Lesion Differential Diagnosis

Ophthalmology Notes

We do our best to simplify ophthalmology in Short Notes and exchange practical experiences between ophthalmologists all over the world.

Recently Published Stories

Optic Disc Swelling

Bilateral Optic Disc Swelling for DD

Bilateral Optic Disc Swelling for DD By Dr.Ahmed Ali What do you think about these photos of a young male

Macular edema in Retinal vein occlusion

Macular edema in Retinal vein occlusion

Macular edema in Retinal vein occlusion By Dr.Ahmed Saleh‎  Macular edema in vein occlusion Is there any protocol to treat?

Operculated Retinal Tear

Operculated Retinal Tear

Operculated Retinal Tear By Dr. Ameen Marashi‎ 35 years old complaining from floaters .What is your Diagnosis and Management? By

Retinal Capillary Haemangioma

Retinal Capillary Haemangioma

Retinal Capillary Haemangioma By Dr.Ameen Marashi‎ Young female What is your Diagnosis ? By Dr.Ahmad Ateya haemangioma By Dr.Ameen Marashi Treated

Retinal Ischeamia

Retinal Ischeamia

 Retinal Ischeamia By Dr.Ameen Marashi‎ Describe what you see and what is your approach ?!! By Dr.Reena Sorokhaibam Capillary non

Age Related Macular Degeneration ( ARMD without CNVM )

Age Related Macular Degeneration ( ARMD without CNVM )

Age Related Macular Degeneration ( ARMD without CNVM ) By Dr.Ameen Marashi‎ This 73 years old patient suffers from reduced

Causes of Papilledema

Causes of Papilledema

Causes of Papilledema Papilledema is an optic disc swelling that is secondary to elevated intracranial pressure. In contrast to other causes

Choroidal Nevus

Choroidal Nevus

Choroidal Nevus By Dr.Ameen Marashi‎ This patient has been followed up for many years because of this appearance with VA

Retinal Diseases Signs In One Picture

Retinal Diseases Signs In One Picture

Retinal Diseases Signs In One Picture Bone spicule pigments (BSP): are a hallmark of retinitis pigmentosa (RP)   Chorioretinal Atrophy:

Cytomegalovirus ( CMV )retinitis

Cytomegalovirus ( CMV )retinitis

Cytomegalovirus ( CMV )retinitis By Dr.Ameen Marashi‎ 40 years old patient suffers from acquired immune deficiency What is the Diagnosis