CURRENT AMD REFERRAL PATHWAYS

The Royal Australian and New Zealand College of Ophthalmologists’ (RANZCO) updated Referral Pathway for AMD Management, highlights the important role optometrists play in monitoring patients with early and intermediate AMD.8 [The document is available on the RANZCO website at: ranzco.edu/home/health-professionals/referral-pathway-foramd-management.] Both the RANZCO referral pathway as well as the Optometry Australia Clinical Practice Guide (CPG) for the Diagnosis and Management of AMD emphasise the importance of optometrists taking an adequate history, performing a suitable clinical examination and diagnostic imaging, and grading AMD using the Beckman Classification (Table 1).4,8

Table 1. Beckman Classification of AMD, adopted from CPG.4

Case history tailored to AMD patients includes eliciting symptoms and risk factors that may be suggestive of AMD, such as age, smoking, and family history. Fundus examination, colour fundus photography (CFP), spectral domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) should be performed; or alternatively, patients can be referred to a practice that offers these imaging modalities. The Beckman Classification allows practitioners to standardise AMD staging and subsequently tailor advice and review periods to the level of disease. A simplified severity scale from the Optometry Australia CPG can also be used to further stratify risk for progression to late AMD, with risk factors being assigned to the presence of significant clinical features (Table 2).4

REFERRAL FOR TREATMENT

Intravitreal anti-VEGF injections have been available in Australia for many years for treatment of neovascular AMD (nAMD). It has been well-established that the presence of macular fluid or haemorrhage on SD-OCT scanning with new-onset visual symptoms warrants a prompt referral to ophthalmology (within one to two weeks) for treatment.4,8 However, there have historically been limited treatment options for early and intermediate AMD. Optometry-led management and education for these patients is paramount. Review periods should be set appropriately, in line with the severity of disease and risk of progression, as per Tables 1 and 2. Lifestyle changes such as smoking cessation and diet should be discussed; AREDS2 antioxidant supplements should be considered in patients with intermediate AMD; and Amsler self-monitoring tools provided.4 Moreover, optometrists should have appropriate discussions with patients regarding driving suitability, family testing, patient support – through organisations such as Macular Disease Foundation Australia (MDFA) or SeeWay (a Guide Dog initiative) – and/or vision rehabilitation services.

Table 2. Five-year risk of progression to late AMD, adopted from CPG.4

Assign one risk factor for each eye with large drusen; for each eye with pigmentary abnormalities associated with medium drusen; and if neither eye has large drusen but both eyes have medium drusen.

Figure 1. A) SD-OCT of a normal macula. B) offers an enlarged view of the hyper-reflective outer retinal bands within the orange box, and C) uses colours to denote the retinal pigment epithelium (RPE = purple), interdigitation zone (IZ = green), ellipsoid zone (EZ = red) and external limiting membrane (ELM = orange). Adapted from Ross et al.16

Figure 2. The right eye of a patient with intermediate AMD, as imaged with A1) FAF and A2) SD-OCT. Note the presence of multiple confluent large soft drusen (>125 µm diameter) on the SD-OCT scan. The same eye progressed to late AMD over five years, following spontaneous drusen regression. B1) shows relative hypo-autofluorescence in the affected areas, and B2) highlights overlying abnormalities to the external limiting membrane and ellipsoid zone as well as a choroidal hypertransmission defect (white dashed arrow).

Figure 3. Multimodal imaging of reticular pseudodrusen with A) near infrared reflectance and B) SD-OCT scanning. Note that RPD occur in the subretinal space and above the RPE (as denoted by the white arrowheads), thus differentiating it from drusen, which occur in the sub-RPE space.

With intravitreal complement inhibitors now approved in Australia for treatment of geographic atrophy (GA), it is recommended that patients who are both motivated and suitable for potential GA treatments be referred to ophthalmology for further discussion.8 Patients who are potentially at high risk of progressing to late AMD should undergo appropriate baseline diagnostic imaging, including SD-OCT and FAF, or be referred to ophthalmology for assessment. It is worth nothing that some optometrists may not have access to SD-OCT or FAF in practice; and moreover, imaging data is not always readily comparable between equipment at different practices.

If a patient is referred to an ophthalmologist for discussion regarding GA treatments, the patient may be commenced on an intravitreal complement inhibitor; or alternatively, a suitable collaborative care plan with the referring optometrist can be established if a conservative approach and ongoing monitoring is recommended. It is critical for optometrists to understand that intravitreal complement inhibitors do not reverse GA growth but instead slow down progression. Two Phase 3 trials (OAKS and DERBY) found pegcetacoplan (Syfovre, Apellis) slowed GA growth by 19–22% with monthly treatment compared to sham at 24 months; and by 16–18% with every-other-month treatment at 24 months.9 Similarly, GATHER2 showed that avacincaptad pegol (ACP) (Izervay, Astellas) slowed GA growth by 14–19% at 24 months.10

Thus, visual gains are not expected with intravitreal complement inhibitor treatment. Pegcetacoplan is currently indicated for the “treatment of adult patients with GA secondary to AMD with an intact fovea and when central vision is threatened by GA lesion growth”.11 Pooled post-hoc analysis from GATHER1 and GATHER2 showed lower proportions of vision loss with treatment versus sham, suggesting a potential delay in vision loss for patients with foveal-sparing GA.10 In a real-world setting, optometrists are in an ideal position to manage expectations for patients considering GA treatment – specifically, treatment will not restore vision but may slow down the natural progression of GA and delay functional vision loss.

STRUCTURAL BIOMARKERS

To help optometrists further predict the risk of progression to late AMD (and specifically GA) beyond the Beckman Classification and simplified risk severity scoring, interest has turned towards the role of structural biomarkers in diagnostic imaging. A biomarker is defined as “a characteristic that can be objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention”.12 A review and meta-analysis conducted by Trinh and colleagues in 2024 identified some of the key SD-OCT biomarkers that may be predictive of progression to GA and late AMD.13

External Limiting Membrane and Ellipsoid Zone Abnormalities

Along with the retinal pigment epithelium (RPE) and interdigitation zone (IZ), the external limiting membrane (ELM) and ellipsoid zone (EZ) make up the hyper-reflective outer retinal bands (HORB) on a SD-OCT scan (Figure 1). Integrity of the outer retinal bands has long been known to be associated with visual prognosis across a range of macular disease;14,15 however, Trinh and colleagues’ review also found high odds ratios (OR) for progression to GA in eyes with ELM abnormalities (17.34) and EZ abnormalities (6.1).13

Large Drusen and Reticular Pseudodrusen

The presence of large drusen and drusenoid pigment epithelial detachment (dPED) (defined as large drusen with a diameter >350 µm) confers a significant risk for spontaneous drusen regression, resulting in abnormalities to the overlying ELM and EZ.13,17 The volume and number of large drusen appear to be positively correlated with greater risk for progression to late AMD, and drusen regression has been estimated to occur in 50% of eyes with intermediate AMD over five years.17 Figure 2 shows the impact of spontaneous drusen regression over a five-year period.

Reticular pseudodrusen (RPD) describes a drusen variant that occurs in the sub-retinal space (above the RPE) as opposed to sub-RPE. As seen in Figure 3, RPD can be best visualised using SD-OCT and near infrared (NIR) imaging. The presence of RPD, combined with large drusen, has been estimated to increase the risk of progression to late AMD (particularly GA) two- to threefold.13

Hypo-Reflective Drusen Cores

Hypo-reflective drusen cores (HCD) are characterised by uniform hypo-reflectivity within large drusen (Figure 4). They are thought to indicate incipient drusen regression which, as previously mentioned, results in abnormalities to the overlying ELM and EZ.13,17 Thus, the presence of HCD poses significant risk for progression to late AMD and specifically GA, with the hazard ratio for progression to GA calculated to be as high as 2.85.13

Intraretinal Hyper-reflective Foci

Intraretinal hyper-reflective foci (IHRF) are hyper-reflective ‘dot-like’ lesions that occur above drusen in AMD and correlate with pigmentary changes on fundus examination and CFP (Figure 5). IHRF are thought to indicate RPE dysfunction, either through RPE displacement, migration, and / or inflammatory reaction.17 The number of IHRF lesions appears to be positively correlated with progression risk, with a five to 10 times increased risk of progression to GA in eyes with IHRF versus those without.13,17

Figure 4. SD-OCT of multiple large soft drusen in intermediate AMD. Note the prominent hypo-reflective drusen core (white arrowhead) as opposed to the surrounding drusen.

Figure 5. SD-OCT of large soft drusen and a large drusenoid pigment epithelial detachment with associated overlying intraretinal hyper-reflective foci (white arrow).

Figure 6. SD-OCT of nascent GA, with the white arrows highlighting an area of subsidence of the outer plexiform layer. Note the intact RPE in the affected area.

Nascent Geographic Atrophy

Nascent geographic atrophy (nGA) refers to a subsidence of the outer plexiform layer (OPL) and inner nuclear layer (INL), often observed as a hypo-reflective wedge within the OPL (Figure 6). Nascent GA precedes loss of RPE and photoreceptors and is strongly correlated with progression to GA.17 The presence of nGA alone may therefore form the basis of a referral to ophthalmology for discussion around potential treatment,8 given the fairly rapid progression to GA (38% at two years).18 The relatively low prevalence of nGA in AMD eyes does, however, limit its usefulness as a structural biomarker, as does the short duration of time before nGA progresses to full GA (average 11 months).17,19

Choroidal Hypertransmission Defect

Choroidal hypertransmission defects (hyperTD) are an SD-OCT finding in which the choroidal features are relatively more visible due to loss of overlying retina and RPE (Figure 2),13 and are therefore closely related to drusen regression and EZ/ELM abnormalities. Choroidal hyperTD can be observed in cases of both nGA and complete GA.

Figure 7. Fundus autofluorescence examples of A) no hyper-AF junctional zone, B) banded hyper-AF localised to the margins of the GA lesion, and C) extensive hyper-AF extending into the periphery consistent with a diffuse trickling pattern.

Hyper-Autofluorescent Junctional Zone

The presence of a hyper-autofluorescent (hyper-AF) junctional zone around an established GA lesion indicates RPE dysfunction and likely risk of further GA progression. Several studies have shown that the greater and more widespread the hyper-AF, the greater the risk of progression.20 For example, a GA lesion with no hyper-AF junctional zone has been shown to exhibit growth of only 0.38 mm2 per year; however, this increases to 0.81–1.41 mm2 /year for focal and banded FAF patterns wherein the hyper-AF surrounds only the GA lesion; and to 3.02 mm2 / yr in diffuse trickling FAF patterns, where the hyper-autofluorescence extends beyond the GA lesion(s) and into the periphery (Figure 7).20

POTENTIAL BARRIERS TO COLLABORATIVE CARE

Potential barriers to collaborative care of AMD include optometry access to diagnostic equipment and imaging modalities; poor understanding of the benefits (and interpretation) of multimodal imaging; and lack of appropriate systems to facilitate the transfer of clinical information and diagnostic imaging between practices. As previously mentioned, optometry-to-ophthalmology referral, or even inter-optometry referral, may sometimes be required for adequate baseline imaging and subsequent monitoring. Cloud-based systems are already commercially available to help streamline collaborative care between practices,21 although it is important to realise that data between different SD-OCT and FAF equipment may not always be directly comparable.

Ideally, there should also be clear and consistent written communication between optometrists and ophthalmologists regarding the stage and rate-of-progression of disease, current lifestyle modifications (including use of AREDS2 antioxidant suppLements and Amsler grid), patient support and vision rehabilitation services that have been accessed, and current motivation and suitability for GA treatment.

Finally, limitations with structural biomarkers include low detection rates in community optometry (closely related with clinical aptitude), inter-observer variability and, in some cases, low prevalence and /or relatively late presentation of a biomarker relative to the onset of GA, thereby limiting the usefulness of the biomarker.19 As Ly and colleagues summarised in 2018: “There is as yet no accurate, single or combination of biomarkers that is able to reliably identify the eye that will progress from that which will not.”17 Thus, the role of structural biomarkers in the AMD space continues to be an evolving one, with further research required to truly determine the most relevant biomarkers that are clinically meaningful in day-to-day practice. Artificial intelligence will also likely play a role in analysis of diagnostic imaging, to further streamline and quantify risk assessment.19 At the time of writing, identification of structural biomarkers serves as a useful adjunct to conventional risk stratification, with those patients exhibiting high-risk biomarkers potentially benefiting from closer review or earlier referral to ophthalmology for consideration of GA treatment.

EXCLUDING OTHER CAUSES OF MACULAR ATROPHY

Optometrists also play a critical role in differentiating AMD from other macular disease. End-stage atrophic macular disease from non-age-related causes can appear similar to GA in clinical appearance. Historical clinical data such as visual acuity and colour vision, as well as previous multimodal imaging in the form of SD-OCT, CFP, FAF, and NIR, can help differentiate diagnoses. A recent retrospective review showed that out of 1,136 cases formerly diagnosed by ophthalmologists as GA, the misdiagnosis rate was estimated to be 1.9%, with 0.97% representing inherited retinal diseases (IRD) (including pattern dystrophy), 0.70% non-specific atrophy, and 0.26% myopic macular atrophy.22 Optometrists should be vigilant in their history taking and consider patient age, family history, refractive error, detailed history of vision impairment and /or deterioration, and other ocular or systemic treatments when considering a diagnosis of GA. Furthermore, genetic testing may help to further differentiate IRD from GA, and a referral from optometry to ophthalmology may be of benefit in atypical cases.23

CONCLUSION

Given the expected increase in AMD prevalence and the available eye health workforce in Australia, optometrists are expected to play an increasingly important role in managing early-to-intermediate AMD patients through comprehensive clinical examination, multimodal diagnostic imaging, and patient education. Moreover, the availability of intravitreal complement inhibitors in Australia means that optometrists must fully understand the role of GA treatments, be confident in identifying suitable patients, and referring to ophthalmologists appropriately. This must be done in such a way that continues to optimise patient outcomes without overburdening the eye healthcare system. As with all collaborative care models, clear and consistent communication between practitioners will be critical. Relevant scans should be included (with systems allowing for secure transfer of imaging and /or analysis across different health record interfaces), and patient motivation clearly defined. Support services, such as MDFA and SeeWay, offer additional patient support outside of a clinical setting and should be utilised to holistically manage AMD patients.

A survey by Guymer and colleagues in 2025 established that “optometrists want to see patients with GA, are keen to learn more about GA diagnosis and management, and want to have discussions with appropriate patients about treatment and referral options… it is [therefore] important that optometrists prepare for changes in the clinical management for GA”.5 Ongoing optometric education about AMD, diagnostic imaging, and potential treatments for GA will cement the important role of Australian optometrists in providing collaborative care to AMD patients, and ensure “they are best equipped for their role in providing high quality primary eye care to patients with [AMD] and GA”.5

CASE REPORT

75-year-old Bronwyn Grech* presented to her community optometrist in 2021 with numerous large soft drusen and pigment changes in each eye, left greater than right. Additionally, in the left eye she was noted to have ELM and EZ abnormalities, drusenoid PED, and intraretinal hyper-reflective foci (IHRF) (Figures 8 and 9). Mrs Grech was pseudophakic in each eye and visual acuities were R 6/7.5; L 6/12.

Ms Grech was informed that she had intermediate AMD, graded in accordance with Beckman Classification of AMD. As per Table 2, her risk for progression to late AMD in one or other eye within the next five years was estimated to be as high as 50% given the presence of four risk factors (both eyes exhibited pigment changes and large drusen). In accordance with Optometry Australia’s CPG for the Diagnosis and Management of AMD and RANZCO’s Referral Pathway for AMD Management, her optometrist discussed lifestyle and dietary changes, commenced AREDS2 antioxidant supplements, and recommended self-monitoring with an Amsler grid, with instructions to return earlier if there was any new distortion noted. Six-monthly monitoring with serial SD-OCT and FAF was recommended. Ms Grech was reassured that she was still meeting legal requirements for an unconditional private driver’s licence and was offered a referral to MDFA for support, as well as to low vision services. She declined the latter as she was not having any difficulties with daily activities of living.

Ms Grech adhered to the advice provided and attended six-monthly reviews as scheduled. In late 2025, she presented acutely with deterioration of vision in the left eye from 6/12 to 6/60. Repeat SD-OCT showed progression to late AMD in the left eye – there was centre-involving GA with loss of RPE, EZ, and ELM, and corresponding choroidal hyperTD greater than 250 µm in diameter. FAF confirmed a hyper-autofluorescent (hyper-AF) lesion with banded hyper-AF (Figure 11). OCT-angiography (OCT-A) excluded nAMD in the left eye. At this point, Ms Grech elected to be referred to both SeeWay and low vision services for assessment for adaptive technology to help with reading. While the visual acuity was still 6/7.5 in the right eye, the optometrist astutely noticed subtle drusen regression and EZ abnormalities compared to baseline imaging in 2021, raising concern around the possibility of eventual progression to GA on this side (Figure 10). Ms Grech was motivated to preserve the vision in the better-sighted right eye, and she was therefore referred to an ophthalmologist for discussion regarding potential GA treatments.

*Name changed for patient anonymity. Production of this article was sponsored by Astellas.

References available at mieducation.com.