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The Intermediate AMD Gap

~35-40%

are intermediate stage

~100,000 today, ~160,000 in 20 years time

AREDS-2 supplements

"Watch and Wait"

At Hamilton Eye Clinic — two treatments for these patients:

�2RT Subthreshold Laser to reduce risk of progression, and - ‘coming soon’ - MacuMira to improve vision

Worsley & Worsley, NZMJ 2015 (updated 2026); Wong et al. Lancet Glob Health 2014

Māori or Pacifica not estimated

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Optometry at the Forefront

Gatekeepers

First Contact

Control Access

Triage

This Evening’s Talk:

Stage the patient

Calculate risk of Late AMD

2RT – since 2013

Who to refer — and for which Rx

Introduce MacuMira

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Staging AMD

Early

Medium drusen (63–125 µm)

No pigment changes

Intermediate

Large drusen (≥125 µm) and/or Pigment changes

Late

Geographic atrophy or

Neovascular AMD

OCT Is Essential

Stageable in 97.7% vs 52.4% with photos alone.

Midena et al. PLoS One 2020; Ho et al. Ophthalmic Physiol Opt 2024; Agrón et al. AREDS Report 42, 2024

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Risk Stratification — The AREDS Simplified S

How to Score (Each Eye)

Within 2 disc diameters of the fovea:

1 pt

Large drusen (≥125 µm)

1 pt

Pigmentary changes

2 pts

Advanced AMD in other eye

Sum both eyes → Score 0–4

≈125 µm ≈ width of retinal vein at the disc margin

5-Year Progression to Late AMD

0.5%

12%

26%

50%

AREDS Score

The disease is a continuum

AREDS Report 18 (2005)

Low risk

High risk

Risk Stratification — The AREDS Simplified Severity Scale

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Score 0

0.5%

RPD adds risk – Small but Risky

AREDS Report 42 (2024) — the severity scale updated by RPD status

5-Year Risk of Progression to Late AMD

Without RPD

With RPD

Score 1

12%

29%

Score 2

26%

59%

Score 3

50%

72%

Score 4

Key Points

RPD is an independent risk feature

Under-recognised in practice — actively look on HR-OCT, FAF, and NIR

RPD isn’t the only additional feature with a major effect on risk — soft drusen load matters too.

AREDS Report 42 (2024)

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DPED

~100%

10 year risk

Drusen load is additional risk – Big is Risky

The AREDS scale treats all drusen ≥125 µm the same — but risk increases continuously with size

5-Year Risk of Late AMD by Drusen Size

0.3%

Small

<63 µm

~4%

Medium

63–125 µm

~12%

Large

125–250 µm

~40%

Very Large

≥250 µm

~67%

DPED

≥433 µm

Very large drusen and DPED are very high-risk intermediate AMD patients — refer for before they progress.

Cukras et al. AREDS2 Report 17, 2019; AREDS Report 28, 2010; de Amorim Garcia Filho et al. IOVS 2015; Roquet W et al. BJO 2004

Low risk

High risk

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How Risk Builds — AREDS Score + RPD + Drusen Load

Each layer of features adds risk. The same AREDS score can mean very different things.

No RPD

With RPD

AREDS Score 2

AREDS Score 3–4

4×

range

12%

Large drusen

(125–250 µm), no RPD

25%

Very large drusen (≥250 µm)

no RPD

29%

Large drusen (125–250 µm) + RPD

50%

Very large drusen (≥250 µm)

+ RPD

26%

Large drusen

± pigment

no RPD

59%

Large drusen

± pigment

+ RPD

67%

DPED

(≥433 µm)

72%

Score 4 + RPD

Fellow eye late AMD

A score-2 patient with very large drusen + RPD has nearly twice the risk of some score-3 patients

AREDS Report 18, 2005; Agrón et al. AREDS Report 42, 2024; Cukras et al. AREDS2 Report 17, 2019; Liew et al. 2016

This is the slide that should change how optometrists think about risk.��TEACHING SEQUENCE:�1. Point to the left column: 'All four of these patients have AREDS score 2. But look at the range.'�2. Point to the orange bracket: '12% to 50% — a four-fold range within the SAME score.'�3. Point to the dashed crossover line: 'This score-2 patient at the bottom — 50% risk — has HIGHER risk than this score-3 patient at the top — 26%. The score alone doesn’t tell you enough.'�4. Land on the teal bar: 'This is why I’m asking you to look beyond the score. Assess drusen size. Look for RPD. Those two features shift the risk more than the score category itself.'��The colour coding: teal bars = no RPD, salmon bars = RPD present. The audience can see at a glance that every salmon bar is longer than its teal counterpart.��TRANSITION TO NEXT SLIDE: 'So now you can calculate the risk. The question is — what do you do with it?'

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Communicating Risk to the Patient

Use natural frequencies, not percentages — frame the stage, give them agency

The Approach

“Your macular degeneration is at an intermediate stage. Your vision is still good, but I can see changes that put you at higher risk of it getting worse.

Roughly 3 in every 10 people with eyes like yours will develop the more serious form within 5 years. That means 7 out of 10 won’t — but I want to make sure we do everything we can to keep you in this group.

The important thing is: we have a plan. Take this macular supplement, and I recommend you see a retinal specialist who can assess you for treatments that can reduce that risk/improve your vision.”

Scheffer et al. Surv Ophthalmol 2024; Wang et al. Ophthalmic Physiol Opt 2023; Gigerenzer et al. BMJ 2003

Principles

Natural frequencies: "3 in 10" not "29%"

Name it, frame it, give agency

— what stage, what it means, what we do

Don’t catastrophise, don’t minimise

— honest but normalising

Always lead to action

— supplements, monitoring, referral

Principles

Natural frequencies: "3 in 10" not "29%"

Name it, frame it, give agency

— what stage, what it means, what we do

Don’t catastrophise, don’t minimise

— honest but normalising

Always lead to action

— supplements, monitoring, referral

This slide is about the most important 60 seconds in the patient journey — the moment you tell them their risk.��KEY TEACHING POINT: Use natural frequencies. Gigerenzer's research (BMJ 2003) shows that patients understand '3 in 10' far better than '29%'. Percentages are abstract; natural frequencies are concrete — the patient can picture 10 people and see where they sit.��The script on this slide is for a typical score-2/3 patient with RPD (roughly 29-59% risk). Adjust the natural frequency to the patient's actual risk:�- Score 1, no RPD: 'about 1 in 25' (4%)�- Score 2, no RPD: 'about 1 in 8' (12%)�- Score 2 + RPD: 'about 3 in 10' (29%)�- Score 3 + RPD: 'about 6 in 10' (59%)�- Score 4 + RPD: 'about 7 in 10' (72%)��The pattern is always the same: (1) Name the stage — 'intermediate macular degeneration'. (2) Frame it — 'your vision is still good'. (3) Quantify honestly — use natural frequency. (4) Pivot to action — supplements, monitoring, referral. (5) Give them agency — Amsler grid, lifestyle.��The two things to avoid: saying 'you have macular degeneration' and stopping (terrifies them), or saying 'don't worry about it' (minimises it, patient won't self-monitor). The sweet spot is honest but normalising.��IF TIME IS SHORT: just make the natural frequency point and move on. That single change transforms the patient conversation.

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2RT

Retinal Rejuvenation

Therapy

Two Treatments for Intermediate AMD

2RT – addressing structurally high-risk iAMD since 2013

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Introducing MacuMira

Subsensory microcurrent stimulation for AMD

MacuMira

Subsensory microcurrent (below perception threshold)
Targets RPE mitochondria → reverses progressive RPE decay.

Similar rationale to PBM but different energy delivery

Non-invasive headset — worn over closed eyelids
32-minute sessions

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MacuMira — Clinical Evidence

Trial Design

62 patients (43 treatment, 19 sham)

Protocol:

4 treatments in first 2 weeks

+ 2 further at weeks 14 and 26

(6 treatments total over 30 weeks)

Follow-up:

30 weeks

Outcome	MacuMira (n=43)	Sham (n=19)
ETDRS at 30 weeks	+10.4 letters (95% CI 7.8–13.1, p<0.001)	−2.1 letters from baseline
≥10 letter gainers	48% achieved ≥10 letter gain	0%
Contrast Sensitivity	Similar benefit to VA	No improvement
Adverse Events	0% — no side effects	0%

Interpretation

Effect grew over time

Limitations: Pilot study; small study, short follow-up.

Larger confirmatory trials are underway.

Parkinson KM, Sayre EC, Tobe SW. Int J Retina Vitreous. 2023;9(1):36. ClinicalTrials.gov NCT02540148

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MacuMira — Treatment Protocol

Induction

4 sessions over 4–10 days (32 min each)

Maintenance

1 session every 3 months (ongoing)

Monitoring

OCT + VA + CS at each visit.

Treatment is off-label. Costs TBC.

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Two Treatment Categories — Structure vs Function

Different clinical questions lead to different therapies

CATEGORY 1: Structural Risk → 2RT Laser

Clinical question:

"Is this eye at high-risk of progressing to late AMD?"

Selection criteria:

High central soft drusen load
Pigmentary changes
Fellow eye has late AMD
No VA threshold

RPD phenotype NOT usually offered 2RT

Goal: Prevent progression

CATEGORY 2: Functional Decline → MacuMira

Clinical question:

"Is visual function declining?"

Qualifying criteria (one or more):

VA ≤6/12 (BCVA +/− pinhole)
+/- Reduced contrast sensitivity (formal testing)
+/-Consistent functional symptoms (low-light difficulty, face recognition etc.) supported by clinical findings

Includes RPD phenotype

Goal: Improve visual function

A patient can meet criteria for one category, or both. Structural risk and functional decline are independent clinical questions.

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Combined Therapy — Sequencing 2RT + MacuMira

For patients with high-risk structural features AND functional decline

2RT Laser

Structural risk reduction

Treat the structural threat first.

3 Month Standdown

Retinal remodelling complete.

MacuMira Loading

4 sessions over 4–10 days

MacuMira Maintenance

1 session every 3 months

Why 3 months? Gunawan et al. (CEO 2022) showed structural recovery and functional improvement at stabilized by 3 months post-2RT (p<0.001).

Clinical prudence when combining novel therapies without published combination data.

2RT retreatment: Review at 6–12 months.

Retreatment decision based on structural risk.

Both treatments are self-funded.

Gunawan JR, Thiele SH, Isselmann B, et al. Clin Exp Ophthalmol. 2022;50(1):31–39.

Functional decline

This slide answers: what do you do when a patient has BOTH high structural risk and declining function?��The key message is simple: treat the structural threat first (2RT), wait 3 months, then address the functional decline (MacuMira).��WHY THIS ORDER:�- 2RT targets the disease process (drusen, RPE stress) — if the eye progresses to late AMD, there’s no point treating function.�- MacuMira targets the RPE mitochondria for ATP production — this is about improving what the patient has now.�- Structural stabilisation before functional optimisation is the logical clinical sequence.��WHY 3 MONTHS (detail for Q&A):�Gunawan et al. (CEO 2022) studied post-2RT changes:�- Structural recovery and functional stability at 3 months�- Rod function improved at 3 months (p<0.001)�- BCVA: +1.9 letters at 12 months vs fellow eye (p=0.027)�- No published data on combining 2RT + MacuMira — the 3-month gap is clinical prudence as much as evidence-based.��2RT RETREATMENT:�Review at 6–12 months post-treatment. The retreatment decision is separate from the MacuMira maintenance pathway.��IMPORTANT: Both therapies are off-label and self-funded. This is discussed at the first appointment. Manage expectations — MacuMira improves function in most but not all patients.

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Putting it into practice

From score to strategy — what to do at each risk level

Lower Risk

Score 0–1, no RPD, no large drusen

Routine annual review

Counsel on modifiable risk factors

No supplements indicated

Elevated Risk

Score 2+, or any score with RPD

AREDS2 supplements Amsler grid home monitoring

Educate on symptoms

Consider referral for 2RT and/or MacuMira

High Risk

Score 3–4, very large drusen, DPED, RPD

Refer for 2RT and/or MacuMira

Calculate risk & discuss prognosis

AREDS2 supplements Amsler grid home monitoring

Calculate risk & discuss prognosis

Educate on symptoms

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