- Email: [email protected]
Photopsias: A Key to Diagnosis
Photopsias: A Key to Diagnosis Gary C. Brown, MD, MBA,1,3,4,5 Melissa M. Brown, MD, MBA,2,4,5 David H. Fischer, MD1,3 Purpose: To assess the character and cause of photopsias in vitreoretinal patients. Design: Cross-sectional study. Participants: A total of 169 consecutive patients (217 eyes) with vitreoretinal disease presenting with a history of photopsias. Methods: A total of 217 eyes with photopsias in 169 patients were evaluated. Photopsia assessment included (1) laterality (unilateral, bilateral but not simultaneous, bilateral, and simultaneous); (2) morphology (flash, zig-zag, strobe, scintillating scotoma, twinkling, other); (3) color (white, silver, yellow, combination, other); (4) location (temporal, central, other); (5) duration (quick, prolonged, constant, other); (6) frequency; (7) diurnal appearance (day, night, both); (8) stimuli (turning head or eyes, hypoglycemia, hyperglycemia, other); and (9) associated systemic or ocular signs and symptoms (headache, numbness, weakness, vertigo, syncope, diplopia, hypotension, floaters, other). Main Outcome Measures: Clinical photopsia features correlated with the causes of photopsias. Results: Thirty-two photopsia causes were identified. The top 16 included posterior vitreous detachment (PVD) in 39.7% of eyes; retinal tear in 8.9% of eyes; neovascular age-related macular degeneration (AMD) in 7.9% of eyes; rhegmatogenous retinal detachment (RRD) in 7.5% of eyes; classic and ophthalmic migraine in 6.5% of eyes; hypoglycemia in 2.8% of eyes; vertebrobasilar insufficiency in 2.8% of eyes; non-AMD choroidal neovascularization in 2.3% of eyes; retinitis pigmentosa in 1.9% of eyes; severe cough in 1.9% of eyes; central serous chorioretinopathy in 1.4% of eyes; intraocular lens reflections in 0.9% of eyes; blue field entoptic phenomenon in 0.9% of eyes; Charles Bonnet syndrome in 0.9% of eyes; digitalis in 0.9% of eyes; and metastatic adenocarcinoma to the brain in 0.9% of eyes. The photopsias associated with PVD are typically quick (96%), with lightning/flash morphology (96%), white (87%), temporally located (86%), associated with new-onset floaters (85%), preferentially seen in dark (90%) rather than lighted environments (29%), and often initiated by head/eye movements (60%). Retinal detachment had a similar profile, but with more nontemporal photopsias (40%) (P ¼ 0.01). The photopsias from neovascular AMD are more centrally located (83%), quick and repetitive (79%), seen in light (73%) and dark (63%) environments, have no inciting stimuli (84%), and are more likely to be nonwhite (40%). Conclusions: A pointed history for photopsias can reveal a cause that may not initially seem apparent. Thus, the history can play a key role in management decisions. Ophthalmology 2015;122:2084-2094 ª 2015 by the American Academy of Ophthalmology. Supplemental material is available at www.aaojournal.org. A photopsia is defined as “the perception of light (luminous rays or flashes) that is purely subjective and accompanies a pathologic condition, especially of the retina or brain.”1 An extensive search of the National Library of Medicine database of 24 million medical articles revealed reports dealing with specific causes of photopsias, such as vitreoretinal traction2 and neovascular age-related macular degeneration (AMD).3 Nonetheless, we were unable to find an article that combined the multiple causes and their characteristic clinical features in consecutive patients with photopsia. We believe that this information could be useful for the clinician. For this reason, we undertook a crosssectional study of patients who presented to a vitreoretinal practice with a specific symptom of photopsia.
Methods Consecutive patients who presented to a vitreoretinal practice over a 12-month period were questioned in a standardized, crosssectional fashion. Included were only those who specifically
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2015 by the American Academy of Ophthalmology Published by Elsevier Inc.
related a history of seeing photopsias as part of their chief symptom. Each person was asked about the clinical features associated with the photopsias. Among the photopsia features assessed were (1) morphology (lightning streak or flash, twinkling, sparkles, pulsations, circles, commas, strobes, arcs, pinwheels, scotomata with scintillations on the edges, flares, and others); (2) color (white, sliver, yellow, blue, red, green, orange, purple, or multicolor); (3) laterality (unilateral or bilateral); (4) simultaneous occurrence or not for bilateral photopsias; (5) location within the visual field (central, temporal, inferior, nasal, superior, combinations, or the entire field); (6) duration (<1 second, seconds, minutes, hours, or longer); (7) frequency of photopsias (hourly, daily, weekly, monthly, or other); (8) observation of photopsias in lighted backgrounds, darkened backgrounds, or both; (9) the presence of stimuli (head turn, eye turn, reading, glucose levels, or other) precipitated the photopsias; or (10) whether systemic or other ocular abnormalities (headache, syncope, vertigo, diplopia, hemihypesthesia, hemiparesis, facial paresthesias, floaters, or others) were associated with the photopsias. In every eye, an examination of the ora serrata was undertaken to look for a retinal tear. In those eyes in which the ora serrata could not be readily seen without scleral depression, 360 scleral http://dx.doi.org/10.1016/j.ophtha.2015.06.025 ISSN 0161-6420/15
Brown et al
Photopsias: A Key to Diagnosis
depression was performed. Biomicroscopic examination of the poster vitreous gel was undertaken with a 60- or 90-diopter lens to assess whether a posterior vitreous detachment (PVD) was present. The diagnosis of PVD was made only if a Weiss ring or partial Weiss ring was present, or if no Weiss ring could be seen but there was a retinal tear or rhegmatogenous retinal detachment (RRD). Optical coherence tomography was not undertaken specifically to make the diagnosis of PVD. A chi-square analysis was used to ascertain differences between different etiologic cohorts. Significance was assumed to occur at a probability <0.05. The study was approved by the Wills Eye Hospital Institutional Review Board.
Results A total of 169 consecutive participants were examined. The demographics of the entire cohort are shown in Table 1. Among the 169 patients were 217 eyes with photopsias (Table 2). A total of 117 patients (70%) had unilateral photopsias (Table 3, available at www.aaojournal.org), and 50 patients (30%) had bilateral photopsias (Table 4). Of the participants with bilateral photopsias, 21 of 50 (42% of bilateral photopsia participants) had simultaneous photopsias, suggesting they were central nervous system in origin. Twenty-nine participants (58%) had bilateral photopsias that occurred at different times, suggesting against central nervous system origin. The mean age was 63 years (standard deviation, 12; 95% confidence interval, 61.3e64.7), and the median age was 63 years. The causes of the photopsias are presented next.
Vitreoretinal Traction Included in this category were 86 eyes with PVD, 19 eyes with retinal tears, 15 eyes with RRD, and 2 eyes with traction retinal detachment, for a total of 122 eyes. Thus, 30% (36/122) of eyes with photopsias occurring as a result of vitreoretinal traction had a retinal tear or retinal detachment. Overall, 28% of eyes (34/122) with vitreoretinal traction or 16% of total eyes (34/217) with photopsias had a retinal tear or RRD. In 85% of eyes (103/122), the photopsias were accompanied by the subjective appearance of new floaters or an increase in floaters. The most common cause of photopsias was PVD, accounting for 39% of overall cases (Table 2), 49% of unilateral cases (Table 3, available at www.aaojournal.org), and 26% of bilateral cases (Table 4). The bilateral flashes from PVD all occurred at different times in different eyes. The photopsias associated with vitreoretinal traction were less than 1 second in length in 95% of eyes (116/122) and had the morphology of a lightning streak or flash in 94% of eyes (114/122) (Table 5). The incidence of these quick lightning streaks/flashes associated with PVD was 96%, with retinal tear was 84%, and with RRD was 86% (P ¼ 0.08). The incidence of white flash color did not differ (P ¼ 0.54) among eyes with PVD (87%) causing photopsias, eyes with retinal tear (79%), or eyes with RRD (80%). The incidence of photopsias occurring primarily in the dark also did not differ (P ¼ 0.74) among eyes with PVD (69%), eyes with retinal tear (63%), and eyes with RRD (60%). Eyes with photopsias with PVD saw flashes in lighted backgrounds in 29% of cases (25/87), whereas those with retinal tears saw the same in 37% of cases (7/19) (P ¼ 0.49). There was no difference between the incidence of seeing photopsias in lighted backgrounds between eyes with PVD/retinal tear (31%) and eyes with retinal detachment (40%) (P ¼ 0.44). The lightning streaks/flashes were subjectively noted to be temporal in 86% of eyes with PVD and 84% of eyes with retinal
tear (P ¼ 0.82). However, eyes with RRD had a 60% incidence of temporal flashes, significantly lower than the combined 86% incidence of temporal flashes noted with eyes with PVD/retinal tear (P ¼ 0.01). Although the incidence of nontemporal, quick white flashes was 40% with eyes with RRD and 14% in PVD/ retinal tear, the overall number of such eyes in our series with PVD/retinal tear (n ¼ 15) still exceeded those with RRD (n ¼ 6) by a ratio of 5:2. There were 2 eyes with photopsias occurring in association with traction retinal detachment and 4 eyes with proliferative retinopathy (1 patient with diabetes and 1 patient with Eales disease) but no visible PVD. Nonetheless, it was presumed that the latter 4 eyes likely had photopsias occurring secondary to vitreoretinal traction, because posterior segment neovascularization appears to stimulate contracture of the overlying vitreous gel.4 The photopsias were all quick, with lightning streak/flash morphology and temporal location. In the 4 eyes without grossly visible vitreoretinal traction, however, the flashes were all yellow (Table 5). This contrasted with the 122 eyes with grossly visible vitreous traction, in which the incidence of yellow flashes was 13% (16/122) (P ¼ 0.002).
Neovascular Macular Degeneration After vitreoretinal traction, the second most common cause of photopsias was neovascular macular degeneration (n ¼ 25 eyes). There were 18 eyes with neovascular AMD and 7 eyes with neovascular macular degeneration occurring secondary to pathology other than AMD (myopic degeneration, angioid streaks, presumed ocular histoplasmosis). In both types, the flashes were centrally located in approximately 80% of eyes versus 18% of vitreoretinal traction cases (P < 0.0001). Although a minority (24%) lasted <1 second, the photopsias lasted seconds or longer in 76% of eyes (P < 0.0001 vs. vitreoretinal traction cases). In one third of neovascular AMD cases, the photopsias were constant, versus none in the eyes with PVD and retinal tear and 7% in eyes with retinal detachment (P < 0.0001). In 96% of cases, the photopsias were described as twinkling, pinwheels, starbursts, strobes, or circles, versus lightning streaks/flashes (92%) in vitreoretinal traction cases (P < 0.0001). Although photopsias Table 1. Demographic Features of 169 Patients with Photopsia Feature Gender Male Female Ethnicity White African American Asian Age: yrs 29e40 41e50 51e60 61e70 71e80 81e90 91þ Mean age ¼ 63 yrs Photopsias Unilateral photopsias Bilateral photopsias Simultaneous Not simultaneous
Patients (n)
Patients (%)
69 100
41% 59%
157 9 3
93% 5% 2%
7 6 40 73 31 11 1 169
4% 4% 24% 43% 18% 7% 1% 100%
117 50 21 29
70% 30% 42% 58%
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Ophthalmology Volume 122, Number 10, October 2015 Table 2. Primary Causes of Photopsias in 217 Eyes
Table 4. Primary Causes of Bilateral Photopsias
Condition
Eyes (n)
Eyes (%)
Condition
Patients (n)
%
PVD, no retinal tear or blood; 2 after intravitreal injection Retinal tear(s) with vitreous detachment Neovascular AMD Retinal detachment, rhegmatogenous Migraine Hypoglycemia Choroidal neovascularization, not AMD Vertebrobasilar insufficiency Retinitis pigmentosa Severe cough with acute respiratory infection Central serous chorioretinopathy Intraocular lens reflections Blue field entoptic phenomenon Charles Bonnet syndrome Traction retinal detachment Proliferative diabetic retinopathy, no retinal detachment, no PVD Hyperglycemia, glucose >400 mg/dl Oral digitalis Metastatic adenocarcinoma to the brain Intravitreal bevacizumab injection Orthostatic hypotension Unilateral migraine Papilledema from pseudotumor cerebri Bilateral acute retinal necrosis Multifocal choroiditis Laser photocoagulation Central retinal vein occlusion Branch retinal vein occlusion Embolic central retinal artery occlusion Embolic branch retinal artery occlusion Toxoplasmosis, chronic Acute idiopathic blind spot enlargement syndrome/acute zonal occult outer retinopathy Adult-onset foveal pigment epithelial dystrophy Unilateral migraine Bests disease Total
86
39.2%
19 18 15 13 6 6 5 4 4 4 2 2 2 2 2
8.8% 8.4% 7.0% 6.0% 2.8% 2.8% 1.9% 1.9% 1.9% 1.9% 0.9% 0.9% 0.9% 0.9% 0.9%
PVD, no retinal tear or blood Migraine, classic and ophthalmic Migraine alone Migraine both eyes, PVD 1 eye Retinal tear(s) Retinal tear bilaterally Retinal tear 1 eye, PVD 1 eye Neovascular AMD Hypoglycemia in insulin-dependent diabetes Retinal detachment Retinal detachment 1 eye, PVD 1 eye Bilateral retinal detachment Vertebrobasilar insufficiency
14 8 6 2 6 5 1 4 3 3 2 1 2 (a third with 1 enucleated eye) 2
28% 16% 12% 4% 12% 10% 2% 8% 6% 6% 4% 2% 4%
2 2 2 2 2 2 2 1 1 1 1 1 1 1 1 1
0.9% 0.9% 0.9% 0.9% 0.9% 0.8% 0.8% 0.5% 0.5% 0.5% 0.5% 0.5% 0.5% 0.5% 0.5% 0.5%
2 1 1 1 1 1 1 1 1 50.0 21 29
4% 2% 2% 2% 2% 2% 2% 2% 2% 100% 42% 58%
1 1 1 217
0.5% 0.5% 0.5% 100.0%
AMD ¼ age-related macular degeneration; PVD ¼ posterior vitreous detachment.
in vitreoretinal traction cases were seen with lighted backgrounds in 31% of eyes (38/123), they were seen in lighted backgrounds in 88% of eyes with neovascular AMD (21/25) (P ¼ 0.003).
Migraine The third leading cause of photopsias after vitreoretinal traction and neovascular macular degeneration was migraine (n ¼ 14 eyes), which occurred in 14 eyes of 8 participants. Photopsias symptoms were bilateral in 6 participants and unilateral in 2 participants, 1 who had only 1 eye. Only 1 person, the 31-year-old who lost an eye to trauma, had classic migraine with an aura (photopsias) followed by a severe headache. The photopsias in all eyes occurred as scintillating scotomas, in which a central blind spot was surrounded by photopsias described as flashes, sparks, solar flares, or zig-zags. Other than 1 person who saw bilateral royal blue ovals surrounded by shimmering gold rims, the photopsias had a component of white in all instances. Red, green, or yellow flashes were blended in with the white in 2 people with bilateral photopsias (31%). The photopsias were constant, lasting 1 to 30
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Severe coughing with upper respiratory infection Retinitis pigmentosa Papilledema, pseudotumor cerebri Blue field entoptic phenomenon Charles Bonnet syndrome Proliferative diabetic retinopathy Metastatic adenocarcinoma to the brain Oral digitalis Hyperglycemia >400 mg/dl Orthostatic hypotension Total Simultaneous bilateral photopsias Nonsimultaneous bilateral photopsias
4%
AMD ¼ age-related macular degeneration; PVD ¼ posterior vitreous detachment. Cases with bilateral simultaneous photopsias are shaded.
minutes, with a mean of 16 minutes. They commonly traveled across the visual field. Three people with bilateral photopsias and normally bilateral good vision thought the photopsias were unilateral until they realized, when asked, that they were unable to read, drive, or see television clearly during the migraine episodes. All eyes of persons with migraine had photopsias seen in both light and dark backgrounds.
Hypoglycemia/Hyperglycemia with Diabetes Mellitus Three people, all with insulin-dependent diabetes, had hypoglycemia with a blood glucose level of 70 mg/dl as the cause of photopsias. There were 3 people with hypoglycemia, for a total of 6 eyes, and one with hyperglycemia, for a total of 2 eyes. Thus, there were a total of 8 eyes if hypoglycemia/hyperglycemia are considered as one group. Their mean age was 58 years, with a range from 38 to 72 years. The photopsias were bilateral, simultaneous, and white, typically resolving as the glucose level normalized. They were observed with both light and dark backgrounds. All were centrally located; in 2 eyes, they were described as flickers, and in 4 eyes, they were described as circles. The circles enlarged as the glucose levels decreased and diminished in size as glucose levels increased. One 47-year-old, insulin-dependent, diabetic participant had bilateral photopsias secondary to hyperglycemia, but not hypoglycemia. He noted diffuse white light in both eyes simultaneously when his serum glucose level exceeded 400 mg/dl. The white light resolved as the glucose level decreased and was not affected by light or dark backgrounds.
Table 5. Most Typical Features of Photopsias Cause (n [ No. of Eyes)
Mean Age, Yrs Laterality Simultaneous* Location
Duration
NA
T: 86% I: 8% C: 8% N: 1% E: 1%
<1 sec: 96% Sec: 2% Min: 2%
Retinal tear (19)
61
U: 95% B: 5%
No
<1 sec: 94% Min: 6%
Neovascular AMD (18)
80
U: 71% B: 19%
No
T: 90% I: 10% C: 5% C: 83% I: 11% T: 6%
Rhegmatogenous retinal detachment (15)
58
U: 87% B: 13%
NA: 0%
T: 60% I: 33% C: 13% E: 7%
<1 sec: 83% Min: 7% Constant: 7%
Migraine (12)
66
B: 100%
100%
C: 55% 5e30 min Moves Mean: 16 min T to C or C to T: 45%
Choroidal neovascularization, not AMD (7)
62
U: 100% NA
C: 72% N: 28%
Seconds: 86% 5 min: 14%
Hypoglycemia (6)
58
B: 100%
100%
C: 100%
Seconds to minutes; stop when glucose increases
Vertebrobasilar insufficiency (1 eye enucleated previously) (5)
81
B: 100%
100%
C: 100%
10 sec to 10 min
<1 sec: 33% Seconds to minutes: 33% Constant: 33%
Lightning streak/ flash: 96% Arc: 4% Circle: 4% Stripe: 4% Solar flare: 1% Lightning streak/ flash: 84% Circle: 16% Twinkling: 28% Pinwheel: 17% Starburst: 17% Strobe: 17% Circle: 11% E: 5% Square strobe: 5% Lightning streak/ flash: 73% Streak: 13% Twinkling: 7% Pinwheel: 7% Scintillating scotoma with surrounding sparks, sparkles, or zig-zags: 92%, Flashing entire field: 8% Twinkling/ sparkles: 72% Circle: 14% Lightning: 14%
White: 87% Yellow: 14% Silver: 4% Purple: 1% Black and white: 1% White: 79% Silver: 16% Yellow: 5% White: 61% Blue: 17% Red/green: 11% Green: 6% Multicolored: 6%
Flickering: 33% Central circle: 67%, enlarges as glucose decreases Broken flashes: 40% 15 sec Flashes: 40% Windmill blades: 20%
Diurnal Symptoms
Stimuli
Systemic Associations/Other New floaters: 85%
Daily: 60% Weekly: 29% Monthly: 5% 1 time: 5% Reading: 1%
Dark: 67% Light: 6% Both: 23% 1 time: 5%
Head/eye turn: 60% None: 36% Shut eyes: 2% Reading: 1%
Daily: 68% Weekly: 26% Monthly: 5% Daily: 56%, Constant: 6%, Weekly: 28%, Yearly: 11%
Dark: 63% Light: 16% Both: 21% Light: 29%, Dark: 22%, Both: 44%, Constant: 6%
Head/eye turn: New floaters: 90% 72% None: 28% Reading or TV: None 5% each Shutting eyes or bending: 11% each
White: 80% Yellow: 20% Gold: 7%
Daily: 87% 1 time: 13%
Dark: 60% Light: 20% Both: 20%
Head/eye turn: 73% None: 27%
New floaters: 87%
White/silver: 85%, Blue: 16%, Red, gold, or blue with white: 31% White: 86% Blue: 14%
Weekly: 18% Monthly to months: 45%: 1 time: 36%
Light and dark
None
None
Daily: 71% 1e2/mo: 29%
Light and dark
None
White: 100%
Glucose <70 mg/dl: 100%
Light and dark
Glucose <70 mg/dl: 100%
Note: peripheral choroidal neovascularization opposite to flashes in 2 cases Diabetes: insulin dependent
White: 60% Multicolored: 40%
Daily: 50% Light and None Every 3 mo: 50% dark: 80% Light: 20%
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Vertigo: 100% Dizziness: 100% Syncope: 50% Headache: 50%, with or after photopsia, Cardiac arrhythmia: 50% (Continued)
Photopsias: A Key to Diagnosis
U: 95% B: 5%
Frequency
63
Color
Brown et al
PVD (86)
Morphology
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Table 5. (Continued.) Cause (n [ No. of Eyes)
Mean Age, Yrs Laterality Simultaneous* Location
Duration
Morphology
Diurnal Symptoms
Frequency
Stimuli
Lightning streak: 50% Sparkles: 50% Circle: 50% Arc: 50% Lightning: 50% Flickering or twinkling: 100% Diffuse light, no flashing
White: 100%
Only with severe cough
White: 100%
Hard blinks: 50% Light and dark
White: 100%
Daily to 3/wk
Light and None dark 100%
White: 100%
Light and dark
White: 100%
When serum glucose >400 mg/dl Daily
Severe coughing (4)
56
B: 100%
50%
T: 100%
<1 sec: 50% 15 sec: 50%
Retinitis pigmentosa (4)
43
B: 100%
No
C: 100%
Seconds: 50% Constant: 50%
Central serous chorioretinopathy (3) Hyperglycemia >400 mg/dl (2)
41
U
NA
C: 100%
<1 sec to several seconds
47
B: 100%
100%
E: 100%
10 min
46
B: 100%
100%
C: 100%
5 min
Light bulb flash
74
B: 100%
100%
C: 100%
Minutes
Traction retinal detachment (2)
64
B: 100%
No
<1 sec
Dark: 100%
None
Charles Bonnet syndrome (2)
65
B: 100%
100%
C: 100% T: 100% N: 50% In blind spot: 50% T: 100%
Repetitive diffuse Yellow: 100% Daily flashing Lightning White: 100% Daily
20e30 small white circles
Light and dark
None
Entoptic phenomenon (2)
58
B: 100%
No
C: 100%
Proliferative retinopathy, diabetic, no PVD seen (2) Proliferative retinopathy, idiopathic, no PVD seen (2) Intraocular lens reflections (2)
37
B: 100%
No
T: 100%
37
B: 100%
No
T: 100%
<1 sec
Stripe
Yellow: 100% Daily
Light and dark
79
U
No
C: 100%
<1 sec
Lightning streak
White: 100%
When light hits the eye
Light and dark
58
U
NA
E: 100%
Constant 5 hrs after Repetitive flash: injection 100%
White: 100%
Constantly repetitive 5 hrs: 100%
Metastatic adenocarcinoma to the brain (2) Digitalis toxicity (2)
Intravitreal bevacizumab injection (2)
Seconds
White: 100%
Daily
Light and dark
Light and dark
Severe cough
Systemic Associations/Other None
None
When serum When serum glucose >400 glucose >400 mg/ mg/dl dl None Metastatic adenocarcinoma
Light: 100% None
<1 sec, repetitive over 10e30 dots Silver: 100% When looking at Light: 100% Looking up at seconds to minutes moving in light colors light sky haphazard (white directions, computer coincident with screen, clouds, the heartbeat blue or gray sky) <1 sec Stripe Yellow: 100% Weekly Light and None dark None
Digitalis use, atrial fibrillation Proliferative diabetic retinopathy OU Proliferative diabetic retinopathy OU None
None
None
Entering lighted None room from dark Light: 100% Intravitreal Bilateral choroidal bevacizumab neovascularization injection
Ophthalmology Volume 122, Number 10, October 2015
Color
Table 5. (Continued.) Cause (n [ No. of Eyes)
Mean Age, Yrs Laterality Simultaneous* Location
Duration
Morphology
Color
B: 100%
Yes
E: 100%
Seconds
Unilateral ophthalmic migraine (2) Papilledema, from pseudotumor cerebri (2) Bilateral acute retinal necrosis (1) Multifocal choroiditis (1) Laser photocoagulation (1)
69
U
NA
C
Minutes
Multicolored: Diffuse 100% twinkling several seconds Pulsating light White
73
B: 100%
No
C: 100%
<1 sec
Twinkling
59
U
NA
Left to right
<1 sec
30
U
NA
C
<1 sec
53
U
NA
Central retinal vein occlusion (1)
67
U
NA
Several seconds IT, 180 opposite fundus laser C Constant
Branch retinal vein occlusion (1) Central retinal artery occlusion, embolic (1) Branch retinal artery occlusion, embolic (1) Toxoplasmosis, chronic (1) Acute zonal occult outer retinopathy/ acute idiopathic blind spot enlargement syndrome (1) Adult-onset foveal pigment epithelial dystrophy (1) Best’s disease (1)
52
U
NA
T
71
U
NA
55
U
52
Stimuli
Systemic Associations/Other
Blood pressure Light and <60/30 mmHg dark
Decreased blood Blood pressure pressure <60/30 mmHg
3/wk to monthly Light and dark
None
None No headache
White
Daily
Light and dark
None
None
Circle
White
Daily
Light
None
None
Strobe, repetitive
Whitish-green Constant
None
None
Several second flash
Black and white
Daily
Light and dark Light and dark
Closing eyes
None
Purple
Constant
Light and dark
None
None
<1 sec
Brilliant cross shape continuously flashing Lightning streak
White
Repetitive
None
None
E
Several seconds
Lightning streak
Purple, Two episodes, 3 then orange hrs apart
Light and dark Light and dark
None
None
NA
C
White with purple hue
Constant
Light and dark
None
None
U
NA
I
5 min of light, then 2 Constant flash hrs of flashes within central blurring 1e2 sec Glittering arc
White
Weekly
None
None
29
U
NA
In blind spot
Several seconds
Twinkling
White
Daily
Light and dark Dark
None
None
81
U
NA
C
Hours
Sparkles
Yellow
2/wk
Dark and light
Shutting eyes
None
53
U
NA
C
Constant
Twinkling
White-blue
Constant
Dark and light
None
None
o
65
Diurnal Symptoms
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Hypotension, orthostatic (2)
Frequency
Photopsias: A Key to Diagnosis
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AMD ¼ age-related macular degeneration; B ¼ bilateral; C ¼ central; E ¼ entire field; I ¼ inferior; IT ¼ inferotemporal; M ¼ medial; N ¼ nasal; NA ¼ not applicable; OU ¼ both eyes; PVD ¼ posterior vitreous detachment; S ¼ superior; T ¼ temporal; U ¼ unilateral. Numbers may not add to 100% because of rounding or >1 parameter per eye. *Relevant only if bilateral, not applicable if unilateral.
Ophthalmology Volume 122, Number 10, October 2015 Table 7. Photopsia Features Commonly Associated with Different Causes Feature Photopsia Morphology Scintillating scotoma Lightning streak Pulsating silver dots, coincident with heartbeat, 10e30 moving randomly against a light background Nontemporal, lightning streak Central sparkles, twinkling, or strobes Central or diffuse flickering Photopsia Duration <1 sec Several seconds to minutes 1e30 min Photopsia Color Yellow Blue/green/red/gold Purple Silver Silver/white Photopsia Location Temporal Central In blind spot Photopsia Laterality Bilateral simultaneous Bilateral simultaneous Bilateral simultaneous Bilateral simultaneous Bilateral simultaneous Bilateral simultaneous Bilateral simultaneous Unilateral: 81%; bilateral nonsimultaneous: 19% Diurnal Pattern Light only Dark, predominantly Stimuli Head (eye) turn Blood flow diminution Diabetes mellitus with glucose fluctuations Mechanical Systemic Associations Diabetes mellitus Pharmaceuticals Malignancy Headache after scintillating scotoma Headache before or during photopsias Vertigo, syncope
Causes 91% of migraine cases 92% of vitreoretinal traction cases (inner retinal stimulation) Entoptic phenomena 59% (10/17) of traction and RRDs 81% of cases (30/37) with direct outer retinal stimulation (neovascular macular degeneration, retinitis pigmentosa, multifocal choroiditis, Best’s disease, adult-onset foveal pigment epithelial dystrophy, papilledema) Systemic causes (hypoglycemia, hyperglycemia, digitalis, orthostatic hypotension) 98% of vitreoretinal traction cases 33% of neovascular macular degeneration cases 100% of migraine cases Digitalis toxicity, 20% of RRDs, 14% of PVDs, 100% of proliferative retinopathies without PVD Migraine and neovascular macular degeneration, although white is the predominant color for both Retinal artery occlusion, retinal vein occlusion Entoptic phenomenon Vitreoretinal traction PVD, retinal tear Neovascular macular degeneration, vertebrobasilar insufficiency, inherited and inflammatory retinochoroidal diseases Acute zonal occult outer retinopathy/acute idiopathic blind spot enlargement syndrome Migraine Drug-induced Vertebrobasilar insufficiency Hypoglycemia, hyperglycemia Coughing-induced Charles Bonnet syndrome Entoptic phenomena Vitreoretinal traction Intraocular lens reflections, entoptic phenomenon, digitalis Vitreoretinal traction, vertebrobasilar insufficiency Vitreoretinal traction Orthostatic hypotension, ocular ischemic syndrome Hypoglycemia, marked hyperglycemia Severe coughing Hypoglycemia, severe hyperglycemia, traction retinal detachment vitreoretinal traction Digitalis, quetiapine, imatinib (Gleevec, Novartis AG, Basel, Switzerland), ivabradine, voriconazole, paclitaxel, klofelin Cerebral metastasis, cancer-associated retinopathy, and melanoma-associated retinopathy Migraine, vertebrobasilar insufficiency Vertebrobasilar insufficiency Vertebrobasilar insufficiency
PVD ¼ posterior vitreous detachment; RRD ¼ rhegmatogenous retinal detachment. Vitreoretinal traction includes PVD, retinal tear, RRD, and traction retinal detachment.
Vertebrobasilar Insufficiency Three people had photopsias occurring secondary to vertebrobasilar insufficiency (n ¼ 5 eyes). Their mean age was 81 years,
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with a range from 78 to 86 years. The photopsias were bilateral, although 1 patient had previously lost 1 eye from an injury. Of the photopsias, 60% were white and 40% were multicolored. The photopsias were all located centrally and lasted 10 seconds to 10
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Photopsias: A Key to Diagnosis
minutes. They were described as flashes or broken flashes in 80% of patients and windmill blades in 20% of patients. Unlike other causes of photopsias, each patient with vertebrobasilar insufficiency had a history of recent vertigo and dizziness, with 66% having syncope and 66% having moderate to severe headache, the latter usually posterior or on top of the head. The photopsias did not routinely appear just before the headaches, as would be expected for classic migraine. None had diplopia or long-term symptoms and signs, such as hemihypesthesia or hemiparesis. One patient had a cardiac arrhythmia that was questionably contributory.
Severe Coughing Two people experienced bilateral, white, temporal flashes with severe coughing episodes (n ¼ 4 eyes). In 1 person, they were simultaneous, and in the second person they occurred bilaterally, but at different times. The photopsias lasted from <1 second to 15 seconds. Although neither person had an obvious PVD, the possibility that vitreoretinal traction secondary to violent shifting of the vitreous gel was considered as a possible cause.
Retinitis Pigmentosa Two people with retinitis pigmentosa (n ¼ 4 eyes) saw multiple, centrally located, small, white flashes bilaterally and simultaneously. These were present in both lighted and dark environments, and occurred constantly in both eyes of 1 person. In the second person, they lasted <1 second but occurred many times daily. The second person could routinely initiate photopsias by blinking hard, perhaps suggesting the elicitation of phosphenes.
Central Serous Chorioretinopathy Three women with a mean age of 43 years had unilateral photopsias they described as white flickers, centrally located, and lasting for <1 second to several seconds in both light and dark backgrounds (n ¼ 3 eyes). The photopsias occurred daily to 3 times per week. In each affected eye, there was a shallow serous detachment of the sensory retina involving the macular region, with accompanying areas of both retinal pigment epithelial loss and hyperplasia.
Miscellaneous Causes The characteristics of all eyes with photopsias, as well as their specific causes, are shown in Table 5. Digitalis toxicity had the feature of causing bilateral, repetitive yellow flashing, the yellow color having been previously described with digitalis use.5 Although Charles Bonnet syndrome is typically associated with multicolored formed visual hallucinations, 1 person described 20 to 30 small white circles that occurred in between other classic Charles Bonnet syndrome images of faces, people, and flowers. The patient with flashing lights due to the entoptic phenomenon was discovered by a careful history that revealed multiple small, silver-gray commas that moved close to the central field only in a very light background. These photopsias traveled in a pulsatile fashion coincident with the heartbeat. Intraocular lens reflection occurred in 2 people who experienced white flashes <1 second in duration when they came from the dark into a brightly lit background. The presence of a constant purple flash suggested retinal ischemia, because this was observed with central retinal artery occlusion, central retinal vein occlusion, and branch retinal artery occlusion.6e8 The features of all eyes with photopsias are shown in Table 5.
Origin of the Photopsias Among the 217 eyes, we estimate that 84.2% (181/215) of photopsias occurred primarily as a result of direct retinal stimulation (e.g., vitreoretinal traction, neovascular macular degeneration, and papilledema with surrounding subretinal fluid). Conversely, we believe 10.2% (22/215) of photopsias originated in the central nervous system. These included those caused by migraine, vertebrobasilar insufficiency, Charles Bonnet syndrome, and metastatic adenocarcinoma to the brain. In the remaining 5.6% of eyes (12/215), including photopsias associated with hypoglycemia, hyperglycemia, digitalis, and orthostatic hypotension, we could not be certain whether the photopsias originated in the retina or the brain. We suspect the latter because of the simultaneous bilaterality of each.
Additional Causes A list of conditions that have been observed to cause photopsias in addition to the entities observed in our study is shown in Table 6 (available at www.aaojournal.org).9e46 Among the diagnoses we did not encounter in our study cohort were autoimmune retinopathies, including melanoma-associated retinopathy and cancer-associated retinopathy)9e11; multiple evanescent white dot syndrome14; and drugs such as avabradine,21 variconazole,22 quetiapine,23 poppers,24 klofelin,25 paclitaxel,26 imatinib,27 and sclerosants in microfoam for angiography,28 acute macular neuroretinopathy,29 choroidal metastases,30 benign intracranial hypertension,31,32 photodynamic therapy,33 polypoidal vasculopathy,33 choroidal hemangioma,34 uveal melanoma,38 varied brain lesions,40,42,43 and others also may be etiologic factors.
Discussion Our study demonstrates a wide range of subjective symptoms associated with photopsias, as well as a wide range of associated conditions. The features of the photopsias and accompanying symptoms and signs often suggest the origin.
Vitreoretinal Traction The most common cause of photopsias in patients presenting to a vitreoretinal practice is vitreoretinal traction, accounting for at least 57% of eyes (122/215). The traction on the surface of the retina stimulates affected eyes. We are uncertain why the photopsias are predominantly located temporally, although this could be related to the fact that a major adhesion between the vitreous and the posterior pole is the hyaloid-papillary interface. This is located nasal to the visual axis and therefore might be expected to produce temporal photopsias. As noted previously by Goodfellow et al,2 we found that a nontemporal location for quick white photopsias is associated with a higher incidence of retinal detachment than the case for retinal tear or PVD. Nonetheless, because the number of patients with PVD and retinal tear combined far exceed the number of patients with retinal detachment, it is still more likely that the average patient presenting with nontemporal, white, lightning flashes has a PVD/retinal tear than a retinal detachment. Among all 72 patients with PVD, 14 (19%) had bilateral PVD and bilateral photopsias. Nonetheless, in every
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Ophthalmology Volume 122, Number 10, October 2015 case, the photopsias did not occur concurrently in each eye. Some were as close as seconds apart, but none were simultaneous. Although we cannot be certain, we suspect the photopsias encountered with severe coughing occur secondary to violent lurching of the vitreous gel with subsequent vitreoretinal traction. Because neovascularization of the posterior segment causes contracture of the overlying vitreous gel,4 we suspect vitreoretinal traction is also the mechanism in the 4 eyes with proliferative retinopathy that had not yet developed visible traction retinal detachment or retinoschisis. However, we do not know why the eyes with proliferative retinopathy manifested with yellow photopsias, rather than the white variant encountered in the majority of eyes with vitreoretinal traction.
Neovascular Macular Degeneration Neovascular macular degeneration characteristically produces white central photopsias. Accounting for 12% of study eyes (25/215), these photopsias appear as sparkles, twinkles, pinwheels, starbursts, or strobes, rather than lightning flashes. Brown and Murphy3 noted that 59% of 100 consecutive patients with neovascular AMD experienced photopsias, typically centrally, at some time during their course. Our series may have underestimated the incidence of patients with neovascular macular degeneration because we selected people who spontaneously related a history of photopsias, rather than those in whom a history of photopsias was elicited specifically on questioning.
Migraine Migraine, accounting for 6% of eyes (12/215), is associated with photopsia morphology that differs considerably from what is described with other causes. Migraine, whether classic with a headache or purely ophthalmic with no headache, produces scintillating scotomas that are continuous. It produces photopsias that last for minutes at the edges of an often mobile scotoma. Although headaches often follow the photopsias in younger people, the former are commonly absent in the older population.44 These migraine “attacks” are characteristically bilateral, although patients commonly do not realize this is so until, when questioned, they remember they could not read, drive well, or recognize faces clearly during the episode. We thus question whether the entity of unilateral migraine is a real phenomenon or an entity in which there is underappreciation of photopsias in the second eye. Because migraine theoretically occurs as the result of vasoconstriction in the cerebrum, one would typically expect bilateral involvement. We are uncertain whether spasm and occlusion of the central retinal artery, a branch retinal artery, or the ophthalmic artery are causes in unilateral cases, In our experience, such occlusions typically produce rapid, generalized loss of vision, rather than scintillating scotomas that often travel across the visual field over minutes.6e8
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Anterior and Poster Retinal Stimulation It appears that pathologic entities that stimulate the retina anteriorly (vitreoretinal traction) most typically produce quick, temporal lightning flashes. Although the traction initially occurs on the anterior retina, we presume the photopsias still originate because of photoreceptor stimulation in the outer retina. In contrast, those conditions that stimulate photoreceptors from the posterior side of the retina (neovascular macular degeneration, retinitis pigmentosa, central serous chorioretinopathy, adult-onset foveal pigment epithelial dystrophy, multifocal choroiditis, Best’s disease) more typically produce central sparkles, twinkling, or strobes. We presume that retinal-derived photopsias originate in the photoreceptors, but differ depending on the type of stimulus. Nonetheless, we cannot be certain where the photopsias originate in the retina, because people with no light perception can still induce phosphenes by rubbing their eyes vigorously.45,46 Brain-derived photopsias typically occur as scintillating scotomas with migraine or central white flashes with vertebrobasilar insufficiency. Systemic causes (hypoglycemia, hyperglycemia, orthostatic hypotension, digitalis) tend to produce central or diffuse flickering. We are unsure whether photopsias arising from systemic causes occur primarily as the result of retinal stimulation or stimulation elsewhere along visual pathways in the brain. A photopsia history can be of help with management, especially when the cause of the photopsias in unclear. For example, the presence of accompanying headache, vertigo, and dizziness should raise suspicion of possible vertebrobasilar insufficiency. This is an important diagnosis to make; the authors have observed vertebrobasilar insufficiency leads to severe stroke with the “locked-in” syndrome. The presence of central photopsias suggests against vitreoretinal traction, because they occur in only 8% of such cases. Conversely, the sudden appearance of central twinkling, sparking, or strobes should raise the index of suspicion of choroidal neovascularization, because these photopsia features are present in 83% of cases.
Study Limitations As with any study, ours has potential drawbacks. Our data suggest a low sensitivity for a number of the disease entities (true-positives/(true-positives þ false-negatives) with photopsias, as well as a low specificity (true-negatives/(truenegatives þ false-positives) for a number of entities. In this regard, there may be overlap between different entities. For example, the central, quick, white flickering photopsias are similar with choroidal neovascularization and central serous chorioretinopathy, as are the temporal, quick, white photopsias found with PVD, retinal tears, and severe coughing. Furthermore, there is no gold standard for diagnosis for select diseases in the study. Our patient sample was drawn from a vitreoretinal referral practice. Thus, there may be artificially higher incidences of entities such as retinal detachment and retinal tears versus a series of consecutive patients with photopsias from a nonvitreoretinal practice.
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Photopsias: A Key to Diagnosis
In particular, the location of the photopsias is critical, with temporal photopsias suggesting vitreoretinal tractional phenomena, whereas central photopsias suggest macular diseases (neovascular macular degeneration, central serous chorioretinopathy, Best’s disease), central nervous system abnormalities (migraine, vertebrobasilar insufficiency, metastatic carcinoma), or systemic abnormalities (hypoglycemia, digitalis toxicity). Laterality is also especially helpful in that simultaneous bilateral photopsias suggest central nervous system abnormalities (migraine, vertebrobasilar insufficiency, papilledema, metastatic carcinoma, Charles Bonnet syndrome) or systemic conditions (hypoglycemia, hyperglycemia, severe coughing, orthostatic hypotension, digitalis toxicity). Characteristic patterns and features associated with different causes of photopsias are shown in Table 7. In summary, there is a wide range of variation in the morphology, color, duration, location, inciting stimuli, and accompanying systemic and ocular symptoms associated with photopsias. Although there is a considerable degree of crossover of symptoms, understanding the patterns most commonly associated with specific underlying conditions can help the clinician to ascertain the cause of photopsias with a greater degree of confidence.
References 1. Photopsia definition. Available at: www.merriam-webster. com/medical/photopsia. Accessed April 3, 2015. 2. Goodfellow JF, Mokete B, Williamson TH. Discriminate characteristics of photopsia in posterior vitreous detachment, retinal tears and retinal detachment. Ophthalmic Physiol Opt 2010;30:20–3. 3. Brown GC, Murphy R. Visual symptoms associated with choroidal neovascularization. Photopsias and the Charles Bonnet syndrome. Arch Ophthalmol 1992;110:1251–6. 4. Benson WE, Brown GC, Tasman W, eds. Diabetes and Its Ocular Complications. Philadelphia, PA: Saunders; 1988: 64–89. 5. Oishi A, Miyamoto K, Kashii S, Yoshimura N. Photopsia as a manifestation of digitalis toxicity. Can J Ophthalmol 2006;41: 603–4. 6. Brown GC, Magargal LE, Shields JA, et al. Retinal arterial obstruction in children and young adults. Ophthalmology 1981;88:18–25. 7. Brown GC, Shields JA. Amaurosis fugax secondary to presumed cavernous hemangioma of the orbit. Ann Ophthalmol 1981;l3:1205–9. 8. Brown GC, Magargal LE. Central retinal artery obstruction and visual acuity. Ophthalmology 1982;89:14–9. 9. Heckenlively JR, Ferreyra HA. Autoimmune retinopathy: a review and summary. Semin Immunopathol 2008;3:127–34. 10. Abazari A, Allam SS, Adamus G, Ghazi NG. Optical coherence tomography findings in autoimmune retinopathy. Am J Ophthalmol 2012;153:750–6. 11. Morita Y, Kimura K, Fujitsu Y, et al. Autoantibodies to transient receptor potential cation channel, subfamily M, member 1 in a Japanese patient with melanoma-associated retinopathy. Jpn J Ophthalmol 2014;58:166–71.
12. Schankin CJ, Maniyar FH, Sprenger T, et al. The relation between migraine, typical migraine aura and “visual snow.” Headache 2014;54:957–66. 13. Lommatzsch AP, Gutfleisch M, Dietzel M, et al. Initial clinical experience in the treatment of vitreomacular traction and macular holes with ocriplasmin. Klin Monbl Augenheilkd 2014;231:909–14. 14. Silva RA, Albini TA, Flynn HW Jr. Multiple evanescent white dot syndromes. J Ophthal Inflamm Infect 2012;2:109–11. 15. Cohen SY, Bulik A, Tadayoni R, Quentel G. Visual hallucinations and Charles Bonnet syndrome after photodynamic therapy for age-related macular degeneration. Br J Ophthalmol 2003;87:977–9. 16. Barile GR, Garg A, Hood DC, et al. Unilateral retinopathy secondary to occult primary intraocular lymphoma. Doc Ophthalmol 2013;127:261–9. 17. Verma R, Lalla R. Increased frequency of headache and change in visual aura due to occipital cysticercus granuloma. BMJ Case Rep 2012 Sep 7;2012. pii: bcr2012006919. http:// dx.doi.org/10.1136/bcr-2012-006919. 18. Roos NM, Wiegman MJ, Jansonius NM, Zeeman GG. Visual disturbances in (pre)eclampsia. Obstet Gynecol Surv 2012;67: 242–50. 19. Sagoo MS, Shields CL, Mashayekhi A, et al. Plaque radiotherapy for choroidal melanoma encircling the optic disc (circumpapillary choroidal melanoma). Arch Ophthalmol 2007;125:1202–9. 20. Wiaux C, Landau K, Borruat FX. Unusual cause of bilateral optic disc swelling: POEMS syndrome. Klin Monbl Augenheilkd 2007;224:334–6. 21. Rayan M, Tawfik M, Alabd A, Gamal A. Ivabradine, a novel heart rate slower: is it a sword of double blades in patients with idiopathic dilated cardiomyopathy? Anadolu Kardiyol Derg 2011;11:402–6. 22. Kadikoy H, Barkmeier A, Peck B, Carvounis PE. Persistent photopsia following course of oral voriconazole. J Ocul Pharmacol Ther 2010;26:387–8. 23. Hazra M, Culo S, Mamo D. High-dose quetiapine and photopsia. J Clin Psychopharmacol 2006;26:546–7. 24. Audo I, El Sanharawi M, Vignal-Clermont C, et al. Foveal damage in habitual poppers users. Arch Ophthalmol 2011;129: 703–8. 25. Iankin VV, Vedrova NN, Nefedova IV. Clinical aspects and diagnosis of klofelin poisoning. Klin Med (Mosk) 1990;68:33–5. 26. Seidman AD, Tiersten A, Hudis C, et al. Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. J Clin Oncol 1995;13: 2575–81. 27. Kwon SI, Lee DH, Kim YJ. Optic disc edema as a possible complication of imatinib mesylate (Gleevec). Jpn J Ophthalmol 2008;52:331–3. 28. Cabrera J, Cabrera J Jr, Garcia-Olmedo MA. Sclerosants in microfoam. A new approach in angiology. Int Angiol 2001;20: 322–9. 29. Kuznik-Borkowska A, Cohen SY, Broïdo-Hooreman O, Gaudric A. Acute macular neuroretinopathy. J Fr Ophtalmol 2006;29:319–22. 30. Demirci H, Shields CL, Chao AN, Shields JA. Uveal metastasis from breast cancer in 264 patients. Am J Ophthalmol 2003;136:264–71. 31. Nagata T, Yamashita Y, Hada H, Sogabe T. A case of visual perseveration attack caused by transverse-sigmoid sinus dural arteriovenous fistula. Rinsho Shinkeigaku 2001;41: 498–502.
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Ophthalmology Volume 122, Number 10, October 2015 32. Digre KB, Nakamoto BK, Warner JE, et al. A comparison of idiopathic intracranial hypertension with and without papilledema. Headache 2009;49:185–93. 33. Tuncer S, Demirci H, Shields CL, Shields JA. Polypoidal choroidal vasculopathy following photodynamic therapy for choroidal hemangioma. Eur J Ophthalmol 2009;19: 159–62. 34. Shields CL, Honavar SG, Shields JA, et al. Circumscribed choroidal hemangioma: clinical manifestations and factors predictive of visual outcome in 200 consecutive cases. Ophthalmology 2001;108:2237–48. 35. Law DZ, Yang FP, Teoh SC. Case report of optic disc drusen with simultaneous peripapillary subretinal hemorrhage and central retinal vein occlusion. Case Rep Ophthalmol Med 2014;2014:156178. 36. Nakaya-Onishi M, Okamoto N, Suzuki A, Fukuda M. Report of a patient with aortic dissection evolving into binocular ischemic retinopathy. Graefes Arch Clin Exp Ophthalmol 2000;238:200–2. 37. Haamann P, Kessel L, Larsen M. Monofocal outer retinitis associated with hand, foot, and mouth disease caused by coxsackievirus. Am J Ophthalmol 2000;129: 552–3. 38. Ah-Fat FG, Damato BE. Delays in the diagnosis of uveal melanoma and effect on treatment. Eye (Lond) 1998;12:781–2.
39. Danks JJ, Harrad RA. Flashing lights in thyroid eye disease: a new symptom described and (possibly) explained. Br J Ophthalmol 1998;82:1309–11. 40. Kasten E, Müller-Oehring E, Poggel D, Sabel BA. Chronic visual hallucinations and illusions following brain lesions. A single case study. Fortschr Neurol Psychiatr 1998;66:49–58. 41. Urushitani M, Inoue H, Udaka F, Kameyama M. Monocular photopsia preceding with neovascular glaucoma due to internal carotid artery occlusion; a case report. Rinsho Shinkeigaku 1996;36:481–4. 42. Taguchi K, Akai H, Watanabe M, et al. Subjective visual symptoms and electroencephalographic analysis before and after removal of occipital falx meningioma. Electroencephalogr Clin Neurophysiol 1980;49:162–7. 43. Inafuku T, Sakai F, Sakamoto T, et al. Visual hallucination in the hemianopic field caused by dural arteriovenous malformation. Rinsho Shinkeigaku 1994;34:484–8. 44. Vongvaivanich K, Lertakyamanee P, Silberstein SD, Dodick DW. Late-life migraine accompaniments: a narrative review. Cephalalgia 2014 Dec 12. pii: 0333102414560635. [Epub ahead of print]. 45. Dictionary.com. Available at: http://dictionary.reference.com/ browse/phosphene. Accessed April 26, 2015. 46. Bókkon I. Phosphene phenomenon: a new concept. Biosystems 2008;92:168–74.
Footnotes and Financial Disclosures Originally received: May 4, 2015. Final revision: June 4, 2015. Accepted: June 17, 2015. Available online: August 3, 2015. Manuscript no. 2015-724. 1 Retina Service, Wills Eye Hospital, Jefferson Medical College, Philadelphia, Pennsylvania.
Author Contributions:
2
Overall responsibility: GC Brown, MM Brown, Fischer
3
Abbreviations and Acronyms: AMD ¼ age-related macular degeneration; PVD ¼ posterior vitreous detachment; RRD ¼ rhegmatogenous retinal detachment.
Research Unit, Wills Eye Hospital, Jefferson Medical College, Philadelphia, Pennsylvania.
Mid-Atlantic Retina, Plymouth Meeting, Pennsylvania. 4 Eye Research Institute, Philadelphia, Pennsylvania. 5
Center for Value-Based Medicine, Flourtown, Pennsylvania.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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Conception and design: GC Brown, MM Brown, Fischer Data collection: GC Brown, MM Brown, Fischer Analysis and interpretation: GC Brown, MM Brown, Fischer Obtained funding: Not applicable
Correspondence: Gary C. Brown, MD, MBA, Mid-Atlantic Retina, 4060 Butler Pike, Plymouth Meeting, PA 19462. E-mail: [email protected].
Methods Consecutive patients who presented to a vitreoretinal practice over a 12-month period were questioned in a standardized, crosssectional fashion. Included were only those who specifically
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2015 by the American Academy of Ophthalmology Published by Elsevier Inc.
related a history of seeing photopsias as part of their chief symptom. Each person was asked about the clinical features associated with the photopsias. Among the photopsia features assessed were (1) morphology (lightning streak or flash, twinkling, sparkles, pulsations, circles, commas, strobes, arcs, pinwheels, scotomata with scintillations on the edges, flares, and others); (2) color (white, sliver, yellow, blue, red, green, orange, purple, or multicolor); (3) laterality (unilateral or bilateral); (4) simultaneous occurrence or not for bilateral photopsias; (5) location within the visual field (central, temporal, inferior, nasal, superior, combinations, or the entire field); (6) duration (<1 second, seconds, minutes, hours, or longer); (7) frequency of photopsias (hourly, daily, weekly, monthly, or other); (8) observation of photopsias in lighted backgrounds, darkened backgrounds, or both; (9) the presence of stimuli (head turn, eye turn, reading, glucose levels, or other) precipitated the photopsias; or (10) whether systemic or other ocular abnormalities (headache, syncope, vertigo, diplopia, hemihypesthesia, hemiparesis, facial paresthesias, floaters, or others) were associated with the photopsias. In every eye, an examination of the ora serrata was undertaken to look for a retinal tear. In those eyes in which the ora serrata could not be readily seen without scleral depression, 360 scleral http://dx.doi.org/10.1016/j.ophtha.2015.06.025 ISSN 0161-6420/15
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Photopsias: A Key to Diagnosis
depression was performed. Biomicroscopic examination of the poster vitreous gel was undertaken with a 60- or 90-diopter lens to assess whether a posterior vitreous detachment (PVD) was present. The diagnosis of PVD was made only if a Weiss ring or partial Weiss ring was present, or if no Weiss ring could be seen but there was a retinal tear or rhegmatogenous retinal detachment (RRD). Optical coherence tomography was not undertaken specifically to make the diagnosis of PVD. A chi-square analysis was used to ascertain differences between different etiologic cohorts. Significance was assumed to occur at a probability <0.05. The study was approved by the Wills Eye Hospital Institutional Review Board.
Results A total of 169 consecutive participants were examined. The demographics of the entire cohort are shown in Table 1. Among the 169 patients were 217 eyes with photopsias (Table 2). A total of 117 patients (70%) had unilateral photopsias (Table 3, available at www.aaojournal.org), and 50 patients (30%) had bilateral photopsias (Table 4). Of the participants with bilateral photopsias, 21 of 50 (42% of bilateral photopsia participants) had simultaneous photopsias, suggesting they were central nervous system in origin. Twenty-nine participants (58%) had bilateral photopsias that occurred at different times, suggesting against central nervous system origin. The mean age was 63 years (standard deviation, 12; 95% confidence interval, 61.3e64.7), and the median age was 63 years. The causes of the photopsias are presented next.
Vitreoretinal Traction Included in this category were 86 eyes with PVD, 19 eyes with retinal tears, 15 eyes with RRD, and 2 eyes with traction retinal detachment, for a total of 122 eyes. Thus, 30% (36/122) of eyes with photopsias occurring as a result of vitreoretinal traction had a retinal tear or retinal detachment. Overall, 28% of eyes (34/122) with vitreoretinal traction or 16% of total eyes (34/217) with photopsias had a retinal tear or RRD. In 85% of eyes (103/122), the photopsias were accompanied by the subjective appearance of new floaters or an increase in floaters. The most common cause of photopsias was PVD, accounting for 39% of overall cases (Table 2), 49% of unilateral cases (Table 3, available at www.aaojournal.org), and 26% of bilateral cases (Table 4). The bilateral flashes from PVD all occurred at different times in different eyes. The photopsias associated with vitreoretinal traction were less than 1 second in length in 95% of eyes (116/122) and had the morphology of a lightning streak or flash in 94% of eyes (114/122) (Table 5). The incidence of these quick lightning streaks/flashes associated with PVD was 96%, with retinal tear was 84%, and with RRD was 86% (P ¼ 0.08). The incidence of white flash color did not differ (P ¼ 0.54) among eyes with PVD (87%) causing photopsias, eyes with retinal tear (79%), or eyes with RRD (80%). The incidence of photopsias occurring primarily in the dark also did not differ (P ¼ 0.74) among eyes with PVD (69%), eyes with retinal tear (63%), and eyes with RRD (60%). Eyes with photopsias with PVD saw flashes in lighted backgrounds in 29% of cases (25/87), whereas those with retinal tears saw the same in 37% of cases (7/19) (P ¼ 0.49). There was no difference between the incidence of seeing photopsias in lighted backgrounds between eyes with PVD/retinal tear (31%) and eyes with retinal detachment (40%) (P ¼ 0.44). The lightning streaks/flashes were subjectively noted to be temporal in 86% of eyes with PVD and 84% of eyes with retinal
tear (P ¼ 0.82). However, eyes with RRD had a 60% incidence of temporal flashes, significantly lower than the combined 86% incidence of temporal flashes noted with eyes with PVD/retinal tear (P ¼ 0.01). Although the incidence of nontemporal, quick white flashes was 40% with eyes with RRD and 14% in PVD/ retinal tear, the overall number of such eyes in our series with PVD/retinal tear (n ¼ 15) still exceeded those with RRD (n ¼ 6) by a ratio of 5:2. There were 2 eyes with photopsias occurring in association with traction retinal detachment and 4 eyes with proliferative retinopathy (1 patient with diabetes and 1 patient with Eales disease) but no visible PVD. Nonetheless, it was presumed that the latter 4 eyes likely had photopsias occurring secondary to vitreoretinal traction, because posterior segment neovascularization appears to stimulate contracture of the overlying vitreous gel.4 The photopsias were all quick, with lightning streak/flash morphology and temporal location. In the 4 eyes without grossly visible vitreoretinal traction, however, the flashes were all yellow (Table 5). This contrasted with the 122 eyes with grossly visible vitreous traction, in which the incidence of yellow flashes was 13% (16/122) (P ¼ 0.002).
Neovascular Macular Degeneration After vitreoretinal traction, the second most common cause of photopsias was neovascular macular degeneration (n ¼ 25 eyes). There were 18 eyes with neovascular AMD and 7 eyes with neovascular macular degeneration occurring secondary to pathology other than AMD (myopic degeneration, angioid streaks, presumed ocular histoplasmosis). In both types, the flashes were centrally located in approximately 80% of eyes versus 18% of vitreoretinal traction cases (P < 0.0001). Although a minority (24%) lasted <1 second, the photopsias lasted seconds or longer in 76% of eyes (P < 0.0001 vs. vitreoretinal traction cases). In one third of neovascular AMD cases, the photopsias were constant, versus none in the eyes with PVD and retinal tear and 7% in eyes with retinal detachment (P < 0.0001). In 96% of cases, the photopsias were described as twinkling, pinwheels, starbursts, strobes, or circles, versus lightning streaks/flashes (92%) in vitreoretinal traction cases (P < 0.0001). Although photopsias Table 1. Demographic Features of 169 Patients with Photopsia Feature Gender Male Female Ethnicity White African American Asian Age: yrs 29e40 41e50 51e60 61e70 71e80 81e90 91þ Mean age ¼ 63 yrs Photopsias Unilateral photopsias Bilateral photopsias Simultaneous Not simultaneous
Patients (n)
Patients (%)
69 100
41% 59%
157 9 3
93% 5% 2%
7 6 40 73 31 11 1 169
4% 4% 24% 43% 18% 7% 1% 100%
117 50 21 29
70% 30% 42% 58%
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Ophthalmology Volume 122, Number 10, October 2015 Table 2. Primary Causes of Photopsias in 217 Eyes
Table 4. Primary Causes of Bilateral Photopsias
Condition
Eyes (n)
Eyes (%)
Condition
Patients (n)
%
PVD, no retinal tear or blood; 2 after intravitreal injection Retinal tear(s) with vitreous detachment Neovascular AMD Retinal detachment, rhegmatogenous Migraine Hypoglycemia Choroidal neovascularization, not AMD Vertebrobasilar insufficiency Retinitis pigmentosa Severe cough with acute respiratory infection Central serous chorioretinopathy Intraocular lens reflections Blue field entoptic phenomenon Charles Bonnet syndrome Traction retinal detachment Proliferative diabetic retinopathy, no retinal detachment, no PVD Hyperglycemia, glucose >400 mg/dl Oral digitalis Metastatic adenocarcinoma to the brain Intravitreal bevacizumab injection Orthostatic hypotension Unilateral migraine Papilledema from pseudotumor cerebri Bilateral acute retinal necrosis Multifocal choroiditis Laser photocoagulation Central retinal vein occlusion Branch retinal vein occlusion Embolic central retinal artery occlusion Embolic branch retinal artery occlusion Toxoplasmosis, chronic Acute idiopathic blind spot enlargement syndrome/acute zonal occult outer retinopathy Adult-onset foveal pigment epithelial dystrophy Unilateral migraine Bests disease Total
86
39.2%
19 18 15 13 6 6 5 4 4 4 2 2 2 2 2
8.8% 8.4% 7.0% 6.0% 2.8% 2.8% 1.9% 1.9% 1.9% 1.9% 0.9% 0.9% 0.9% 0.9% 0.9%
PVD, no retinal tear or blood Migraine, classic and ophthalmic Migraine alone Migraine both eyes, PVD 1 eye Retinal tear(s) Retinal tear bilaterally Retinal tear 1 eye, PVD 1 eye Neovascular AMD Hypoglycemia in insulin-dependent diabetes Retinal detachment Retinal detachment 1 eye, PVD 1 eye Bilateral retinal detachment Vertebrobasilar insufficiency
14 8 6 2 6 5 1 4 3 3 2 1 2 (a third with 1 enucleated eye) 2
28% 16% 12% 4% 12% 10% 2% 8% 6% 6% 4% 2% 4%
2 2 2 2 2 2 2 1 1 1 1 1 1 1 1 1
0.9% 0.9% 0.9% 0.9% 0.9% 0.8% 0.8% 0.5% 0.5% 0.5% 0.5% 0.5% 0.5% 0.5% 0.5% 0.5%
2 1 1 1 1 1 1 1 1 50.0 21 29
4% 2% 2% 2% 2% 2% 2% 2% 2% 100% 42% 58%
1 1 1 217
0.5% 0.5% 0.5% 100.0%
AMD ¼ age-related macular degeneration; PVD ¼ posterior vitreous detachment.
in vitreoretinal traction cases were seen with lighted backgrounds in 31% of eyes (38/123), they were seen in lighted backgrounds in 88% of eyes with neovascular AMD (21/25) (P ¼ 0.003).
Migraine The third leading cause of photopsias after vitreoretinal traction and neovascular macular degeneration was migraine (n ¼ 14 eyes), which occurred in 14 eyes of 8 participants. Photopsias symptoms were bilateral in 6 participants and unilateral in 2 participants, 1 who had only 1 eye. Only 1 person, the 31-year-old who lost an eye to trauma, had classic migraine with an aura (photopsias) followed by a severe headache. The photopsias in all eyes occurred as scintillating scotomas, in which a central blind spot was surrounded by photopsias described as flashes, sparks, solar flares, or zig-zags. Other than 1 person who saw bilateral royal blue ovals surrounded by shimmering gold rims, the photopsias had a component of white in all instances. Red, green, or yellow flashes were blended in with the white in 2 people with bilateral photopsias (31%). The photopsias were constant, lasting 1 to 30
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Severe coughing with upper respiratory infection Retinitis pigmentosa Papilledema, pseudotumor cerebri Blue field entoptic phenomenon Charles Bonnet syndrome Proliferative diabetic retinopathy Metastatic adenocarcinoma to the brain Oral digitalis Hyperglycemia >400 mg/dl Orthostatic hypotension Total Simultaneous bilateral photopsias Nonsimultaneous bilateral photopsias
4%
AMD ¼ age-related macular degeneration; PVD ¼ posterior vitreous detachment. Cases with bilateral simultaneous photopsias are shaded.
minutes, with a mean of 16 minutes. They commonly traveled across the visual field. Three people with bilateral photopsias and normally bilateral good vision thought the photopsias were unilateral until they realized, when asked, that they were unable to read, drive, or see television clearly during the migraine episodes. All eyes of persons with migraine had photopsias seen in both light and dark backgrounds.
Hypoglycemia/Hyperglycemia with Diabetes Mellitus Three people, all with insulin-dependent diabetes, had hypoglycemia with a blood glucose level of 70 mg/dl as the cause of photopsias. There were 3 people with hypoglycemia, for a total of 6 eyes, and one with hyperglycemia, for a total of 2 eyes. Thus, there were a total of 8 eyes if hypoglycemia/hyperglycemia are considered as one group. Their mean age was 58 years, with a range from 38 to 72 years. The photopsias were bilateral, simultaneous, and white, typically resolving as the glucose level normalized. They were observed with both light and dark backgrounds. All were centrally located; in 2 eyes, they were described as flickers, and in 4 eyes, they were described as circles. The circles enlarged as the glucose levels decreased and diminished in size as glucose levels increased. One 47-year-old, insulin-dependent, diabetic participant had bilateral photopsias secondary to hyperglycemia, but not hypoglycemia. He noted diffuse white light in both eyes simultaneously when his serum glucose level exceeded 400 mg/dl. The white light resolved as the glucose level decreased and was not affected by light or dark backgrounds.
Table 5. Most Typical Features of Photopsias Cause (n [ No. of Eyes)
Mean Age, Yrs Laterality Simultaneous* Location
Duration
NA
T: 86% I: 8% C: 8% N: 1% E: 1%
<1 sec: 96% Sec: 2% Min: 2%
Retinal tear (19)
61
U: 95% B: 5%
No
<1 sec: 94% Min: 6%
Neovascular AMD (18)
80
U: 71% B: 19%
No
T: 90% I: 10% C: 5% C: 83% I: 11% T: 6%
Rhegmatogenous retinal detachment (15)
58
U: 87% B: 13%
NA: 0%
T: 60% I: 33% C: 13% E: 7%
<1 sec: 83% Min: 7% Constant: 7%
Migraine (12)
66
B: 100%
100%
C: 55% 5e30 min Moves Mean: 16 min T to C or C to T: 45%
Choroidal neovascularization, not AMD (7)
62
U: 100% NA
C: 72% N: 28%
Seconds: 86% 5 min: 14%
Hypoglycemia (6)
58
B: 100%
100%
C: 100%
Seconds to minutes; stop when glucose increases
Vertebrobasilar insufficiency (1 eye enucleated previously) (5)
81
B: 100%
100%
C: 100%
10 sec to 10 min
<1 sec: 33% Seconds to minutes: 33% Constant: 33%
Lightning streak/ flash: 96% Arc: 4% Circle: 4% Stripe: 4% Solar flare: 1% Lightning streak/ flash: 84% Circle: 16% Twinkling: 28% Pinwheel: 17% Starburst: 17% Strobe: 17% Circle: 11% E: 5% Square strobe: 5% Lightning streak/ flash: 73% Streak: 13% Twinkling: 7% Pinwheel: 7% Scintillating scotoma with surrounding sparks, sparkles, or zig-zags: 92%, Flashing entire field: 8% Twinkling/ sparkles: 72% Circle: 14% Lightning: 14%
White: 87% Yellow: 14% Silver: 4% Purple: 1% Black and white: 1% White: 79% Silver: 16% Yellow: 5% White: 61% Blue: 17% Red/green: 11% Green: 6% Multicolored: 6%
Flickering: 33% Central circle: 67%, enlarges as glucose decreases Broken flashes: 40% 15 sec Flashes: 40% Windmill blades: 20%
Diurnal Symptoms
Stimuli
Systemic Associations/Other New floaters: 85%
Daily: 60% Weekly: 29% Monthly: 5% 1 time: 5% Reading: 1%
Dark: 67% Light: 6% Both: 23% 1 time: 5%
Head/eye turn: 60% None: 36% Shut eyes: 2% Reading: 1%
Daily: 68% Weekly: 26% Monthly: 5% Daily: 56%, Constant: 6%, Weekly: 28%, Yearly: 11%
Dark: 63% Light: 16% Both: 21% Light: 29%, Dark: 22%, Both: 44%, Constant: 6%
Head/eye turn: New floaters: 90% 72% None: 28% Reading or TV: None 5% each Shutting eyes or bending: 11% each
White: 80% Yellow: 20% Gold: 7%
Daily: 87% 1 time: 13%
Dark: 60% Light: 20% Both: 20%
Head/eye turn: 73% None: 27%
New floaters: 87%
White/silver: 85%, Blue: 16%, Red, gold, or blue with white: 31% White: 86% Blue: 14%
Weekly: 18% Monthly to months: 45%: 1 time: 36%
Light and dark
None
None
Daily: 71% 1e2/mo: 29%
Light and dark
None
White: 100%
Glucose <70 mg/dl: 100%
Light and dark
Glucose <70 mg/dl: 100%
Note: peripheral choroidal neovascularization opposite to flashes in 2 cases Diabetes: insulin dependent
White: 60% Multicolored: 40%
Daily: 50% Light and None Every 3 mo: 50% dark: 80% Light: 20%
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Vertigo: 100% Dizziness: 100% Syncope: 50% Headache: 50%, with or after photopsia, Cardiac arrhythmia: 50% (Continued)
Photopsias: A Key to Diagnosis
U: 95% B: 5%
Frequency
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Color
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PVD (86)
Morphology
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Table 5. (Continued.) Cause (n [ No. of Eyes)
Mean Age, Yrs Laterality Simultaneous* Location
Duration
Morphology
Diurnal Symptoms
Frequency
Stimuli
Lightning streak: 50% Sparkles: 50% Circle: 50% Arc: 50% Lightning: 50% Flickering or twinkling: 100% Diffuse light, no flashing
White: 100%
Only with severe cough
White: 100%
Hard blinks: 50% Light and dark
White: 100%
Daily to 3/wk
Light and None dark 100%
White: 100%
Light and dark
White: 100%
When serum glucose >400 mg/dl Daily
Severe coughing (4)
56
B: 100%
50%
T: 100%
<1 sec: 50% 15 sec: 50%
Retinitis pigmentosa (4)
43
B: 100%
No
C: 100%
Seconds: 50% Constant: 50%
Central serous chorioretinopathy (3) Hyperglycemia >400 mg/dl (2)
41
U
NA
C: 100%
<1 sec to several seconds
47
B: 100%
100%
E: 100%
10 min
46
B: 100%
100%
C: 100%
5 min
Light bulb flash
74
B: 100%
100%
C: 100%
Minutes
Traction retinal detachment (2)
64
B: 100%
No
<1 sec
Dark: 100%
None
Charles Bonnet syndrome (2)
65
B: 100%
100%
C: 100% T: 100% N: 50% In blind spot: 50% T: 100%
Repetitive diffuse Yellow: 100% Daily flashing Lightning White: 100% Daily
20e30 small white circles
Light and dark
None
Entoptic phenomenon (2)
58
B: 100%
No
C: 100%
Proliferative retinopathy, diabetic, no PVD seen (2) Proliferative retinopathy, idiopathic, no PVD seen (2) Intraocular lens reflections (2)
37
B: 100%
No
T: 100%
37
B: 100%
No
T: 100%
<1 sec
Stripe
Yellow: 100% Daily
Light and dark
79
U
No
C: 100%
<1 sec
Lightning streak
White: 100%
When light hits the eye
Light and dark
58
U
NA
E: 100%
Constant 5 hrs after Repetitive flash: injection 100%
White: 100%
Constantly repetitive 5 hrs: 100%
Metastatic adenocarcinoma to the brain (2) Digitalis toxicity (2)
Intravitreal bevacizumab injection (2)
Seconds
White: 100%
Daily
Light and dark
Light and dark
Severe cough
Systemic Associations/Other None
None
When serum When serum glucose >400 glucose >400 mg/ mg/dl dl None Metastatic adenocarcinoma
Light: 100% None
<1 sec, repetitive over 10e30 dots Silver: 100% When looking at Light: 100% Looking up at seconds to minutes moving in light colors light sky haphazard (white directions, computer coincident with screen, clouds, the heartbeat blue or gray sky) <1 sec Stripe Yellow: 100% Weekly Light and None dark None
Digitalis use, atrial fibrillation Proliferative diabetic retinopathy OU Proliferative diabetic retinopathy OU None
None
None
Entering lighted None room from dark Light: 100% Intravitreal Bilateral choroidal bevacizumab neovascularization injection
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Color
Table 5. (Continued.) Cause (n [ No. of Eyes)
Mean Age, Yrs Laterality Simultaneous* Location
Duration
Morphology
Color
B: 100%
Yes
E: 100%
Seconds
Unilateral ophthalmic migraine (2) Papilledema, from pseudotumor cerebri (2) Bilateral acute retinal necrosis (1) Multifocal choroiditis (1) Laser photocoagulation (1)
69
U
NA
C
Minutes
Multicolored: Diffuse 100% twinkling several seconds Pulsating light White
73
B: 100%
No
C: 100%
<1 sec
Twinkling
59
U
NA
Left to right
<1 sec
30
U
NA
C
<1 sec
53
U
NA
Central retinal vein occlusion (1)
67
U
NA
Several seconds IT, 180 opposite fundus laser C Constant
Branch retinal vein occlusion (1) Central retinal artery occlusion, embolic (1) Branch retinal artery occlusion, embolic (1) Toxoplasmosis, chronic (1) Acute zonal occult outer retinopathy/ acute idiopathic blind spot enlargement syndrome (1) Adult-onset foveal pigment epithelial dystrophy (1) Best’s disease (1)
52
U
NA
T
71
U
NA
55
U
52
Stimuli
Systemic Associations/Other
Blood pressure Light and <60/30 mmHg dark
Decreased blood Blood pressure pressure <60/30 mmHg
3/wk to monthly Light and dark
None
None No headache
White
Daily
Light and dark
None
None
Circle
White
Daily
Light
None
None
Strobe, repetitive
Whitish-green Constant
None
None
Several second flash
Black and white
Daily
Light and dark Light and dark
Closing eyes
None
Purple
Constant
Light and dark
None
None
<1 sec
Brilliant cross shape continuously flashing Lightning streak
White
Repetitive
None
None
E
Several seconds
Lightning streak
Purple, Two episodes, 3 then orange hrs apart
Light and dark Light and dark
None
None
NA
C
White with purple hue
Constant
Light and dark
None
None
U
NA
I
5 min of light, then 2 Constant flash hrs of flashes within central blurring 1e2 sec Glittering arc
White
Weekly
None
None
29
U
NA
In blind spot
Several seconds
Twinkling
White
Daily
Light and dark Dark
None
None
81
U
NA
C
Hours
Sparkles
Yellow
2/wk
Dark and light
Shutting eyes
None
53
U
NA
C
Constant
Twinkling
White-blue
Constant
Dark and light
None
None
o
65
Diurnal Symptoms
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Hypotension, orthostatic (2)
Frequency
Photopsias: A Key to Diagnosis
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AMD ¼ age-related macular degeneration; B ¼ bilateral; C ¼ central; E ¼ entire field; I ¼ inferior; IT ¼ inferotemporal; M ¼ medial; N ¼ nasal; NA ¼ not applicable; OU ¼ both eyes; PVD ¼ posterior vitreous detachment; S ¼ superior; T ¼ temporal; U ¼ unilateral. Numbers may not add to 100% because of rounding or >1 parameter per eye. *Relevant only if bilateral, not applicable if unilateral.
Ophthalmology Volume 122, Number 10, October 2015 Table 7. Photopsia Features Commonly Associated with Different Causes Feature Photopsia Morphology Scintillating scotoma Lightning streak Pulsating silver dots, coincident with heartbeat, 10e30 moving randomly against a light background Nontemporal, lightning streak Central sparkles, twinkling, or strobes Central or diffuse flickering Photopsia Duration <1 sec Several seconds to minutes 1e30 min Photopsia Color Yellow Blue/green/red/gold Purple Silver Silver/white Photopsia Location Temporal Central In blind spot Photopsia Laterality Bilateral simultaneous Bilateral simultaneous Bilateral simultaneous Bilateral simultaneous Bilateral simultaneous Bilateral simultaneous Bilateral simultaneous Unilateral: 81%; bilateral nonsimultaneous: 19% Diurnal Pattern Light only Dark, predominantly Stimuli Head (eye) turn Blood flow diminution Diabetes mellitus with glucose fluctuations Mechanical Systemic Associations Diabetes mellitus Pharmaceuticals Malignancy Headache after scintillating scotoma Headache before or during photopsias Vertigo, syncope
Causes 91% of migraine cases 92% of vitreoretinal traction cases (inner retinal stimulation) Entoptic phenomena 59% (10/17) of traction and RRDs 81% of cases (30/37) with direct outer retinal stimulation (neovascular macular degeneration, retinitis pigmentosa, multifocal choroiditis, Best’s disease, adult-onset foveal pigment epithelial dystrophy, papilledema) Systemic causes (hypoglycemia, hyperglycemia, digitalis, orthostatic hypotension) 98% of vitreoretinal traction cases 33% of neovascular macular degeneration cases 100% of migraine cases Digitalis toxicity, 20% of RRDs, 14% of PVDs, 100% of proliferative retinopathies without PVD Migraine and neovascular macular degeneration, although white is the predominant color for both Retinal artery occlusion, retinal vein occlusion Entoptic phenomenon Vitreoretinal traction PVD, retinal tear Neovascular macular degeneration, vertebrobasilar insufficiency, inherited and inflammatory retinochoroidal diseases Acute zonal occult outer retinopathy/acute idiopathic blind spot enlargement syndrome Migraine Drug-induced Vertebrobasilar insufficiency Hypoglycemia, hyperglycemia Coughing-induced Charles Bonnet syndrome Entoptic phenomena Vitreoretinal traction Intraocular lens reflections, entoptic phenomenon, digitalis Vitreoretinal traction, vertebrobasilar insufficiency Vitreoretinal traction Orthostatic hypotension, ocular ischemic syndrome Hypoglycemia, marked hyperglycemia Severe coughing Hypoglycemia, severe hyperglycemia, traction retinal detachment vitreoretinal traction Digitalis, quetiapine, imatinib (Gleevec, Novartis AG, Basel, Switzerland), ivabradine, voriconazole, paclitaxel, klofelin Cerebral metastasis, cancer-associated retinopathy, and melanoma-associated retinopathy Migraine, vertebrobasilar insufficiency Vertebrobasilar insufficiency Vertebrobasilar insufficiency
PVD ¼ posterior vitreous detachment; RRD ¼ rhegmatogenous retinal detachment. Vitreoretinal traction includes PVD, retinal tear, RRD, and traction retinal detachment.
Vertebrobasilar Insufficiency Three people had photopsias occurring secondary to vertebrobasilar insufficiency (n ¼ 5 eyes). Their mean age was 81 years,
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with a range from 78 to 86 years. The photopsias were bilateral, although 1 patient had previously lost 1 eye from an injury. Of the photopsias, 60% were white and 40% were multicolored. The photopsias were all located centrally and lasted 10 seconds to 10
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Photopsias: A Key to Diagnosis
minutes. They were described as flashes or broken flashes in 80% of patients and windmill blades in 20% of patients. Unlike other causes of photopsias, each patient with vertebrobasilar insufficiency had a history of recent vertigo and dizziness, with 66% having syncope and 66% having moderate to severe headache, the latter usually posterior or on top of the head. The photopsias did not routinely appear just before the headaches, as would be expected for classic migraine. None had diplopia or long-term symptoms and signs, such as hemihypesthesia or hemiparesis. One patient had a cardiac arrhythmia that was questionably contributory.
Severe Coughing Two people experienced bilateral, white, temporal flashes with severe coughing episodes (n ¼ 4 eyes). In 1 person, they were simultaneous, and in the second person they occurred bilaterally, but at different times. The photopsias lasted from <1 second to 15 seconds. Although neither person had an obvious PVD, the possibility that vitreoretinal traction secondary to violent shifting of the vitreous gel was considered as a possible cause.
Retinitis Pigmentosa Two people with retinitis pigmentosa (n ¼ 4 eyes) saw multiple, centrally located, small, white flashes bilaterally and simultaneously. These were present in both lighted and dark environments, and occurred constantly in both eyes of 1 person. In the second person, they lasted <1 second but occurred many times daily. The second person could routinely initiate photopsias by blinking hard, perhaps suggesting the elicitation of phosphenes.
Central Serous Chorioretinopathy Three women with a mean age of 43 years had unilateral photopsias they described as white flickers, centrally located, and lasting for <1 second to several seconds in both light and dark backgrounds (n ¼ 3 eyes). The photopsias occurred daily to 3 times per week. In each affected eye, there was a shallow serous detachment of the sensory retina involving the macular region, with accompanying areas of both retinal pigment epithelial loss and hyperplasia.
Miscellaneous Causes The characteristics of all eyes with photopsias, as well as their specific causes, are shown in Table 5. Digitalis toxicity had the feature of causing bilateral, repetitive yellow flashing, the yellow color having been previously described with digitalis use.5 Although Charles Bonnet syndrome is typically associated with multicolored formed visual hallucinations, 1 person described 20 to 30 small white circles that occurred in between other classic Charles Bonnet syndrome images of faces, people, and flowers. The patient with flashing lights due to the entoptic phenomenon was discovered by a careful history that revealed multiple small, silver-gray commas that moved close to the central field only in a very light background. These photopsias traveled in a pulsatile fashion coincident with the heartbeat. Intraocular lens reflection occurred in 2 people who experienced white flashes <1 second in duration when they came from the dark into a brightly lit background. The presence of a constant purple flash suggested retinal ischemia, because this was observed with central retinal artery occlusion, central retinal vein occlusion, and branch retinal artery occlusion.6e8 The features of all eyes with photopsias are shown in Table 5.
Origin of the Photopsias Among the 217 eyes, we estimate that 84.2% (181/215) of photopsias occurred primarily as a result of direct retinal stimulation (e.g., vitreoretinal traction, neovascular macular degeneration, and papilledema with surrounding subretinal fluid). Conversely, we believe 10.2% (22/215) of photopsias originated in the central nervous system. These included those caused by migraine, vertebrobasilar insufficiency, Charles Bonnet syndrome, and metastatic adenocarcinoma to the brain. In the remaining 5.6% of eyes (12/215), including photopsias associated with hypoglycemia, hyperglycemia, digitalis, and orthostatic hypotension, we could not be certain whether the photopsias originated in the retina or the brain. We suspect the latter because of the simultaneous bilaterality of each.
Additional Causes A list of conditions that have been observed to cause photopsias in addition to the entities observed in our study is shown in Table 6 (available at www.aaojournal.org).9e46 Among the diagnoses we did not encounter in our study cohort were autoimmune retinopathies, including melanoma-associated retinopathy and cancer-associated retinopathy)9e11; multiple evanescent white dot syndrome14; and drugs such as avabradine,21 variconazole,22 quetiapine,23 poppers,24 klofelin,25 paclitaxel,26 imatinib,27 and sclerosants in microfoam for angiography,28 acute macular neuroretinopathy,29 choroidal metastases,30 benign intracranial hypertension,31,32 photodynamic therapy,33 polypoidal vasculopathy,33 choroidal hemangioma,34 uveal melanoma,38 varied brain lesions,40,42,43 and others also may be etiologic factors.
Discussion Our study demonstrates a wide range of subjective symptoms associated with photopsias, as well as a wide range of associated conditions. The features of the photopsias and accompanying symptoms and signs often suggest the origin.
Vitreoretinal Traction The most common cause of photopsias in patients presenting to a vitreoretinal practice is vitreoretinal traction, accounting for at least 57% of eyes (122/215). The traction on the surface of the retina stimulates affected eyes. We are uncertain why the photopsias are predominantly located temporally, although this could be related to the fact that a major adhesion between the vitreous and the posterior pole is the hyaloid-papillary interface. This is located nasal to the visual axis and therefore might be expected to produce temporal photopsias. As noted previously by Goodfellow et al,2 we found that a nontemporal location for quick white photopsias is associated with a higher incidence of retinal detachment than the case for retinal tear or PVD. Nonetheless, because the number of patients with PVD and retinal tear combined far exceed the number of patients with retinal detachment, it is still more likely that the average patient presenting with nontemporal, white, lightning flashes has a PVD/retinal tear than a retinal detachment. Among all 72 patients with PVD, 14 (19%) had bilateral PVD and bilateral photopsias. Nonetheless, in every
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Ophthalmology Volume 122, Number 10, October 2015 case, the photopsias did not occur concurrently in each eye. Some were as close as seconds apart, but none were simultaneous. Although we cannot be certain, we suspect the photopsias encountered with severe coughing occur secondary to violent lurching of the vitreous gel with subsequent vitreoretinal traction. Because neovascularization of the posterior segment causes contracture of the overlying vitreous gel,4 we suspect vitreoretinal traction is also the mechanism in the 4 eyes with proliferative retinopathy that had not yet developed visible traction retinal detachment or retinoschisis. However, we do not know why the eyes with proliferative retinopathy manifested with yellow photopsias, rather than the white variant encountered in the majority of eyes with vitreoretinal traction.
Neovascular Macular Degeneration Neovascular macular degeneration characteristically produces white central photopsias. Accounting for 12% of study eyes (25/215), these photopsias appear as sparkles, twinkles, pinwheels, starbursts, or strobes, rather than lightning flashes. Brown and Murphy3 noted that 59% of 100 consecutive patients with neovascular AMD experienced photopsias, typically centrally, at some time during their course. Our series may have underestimated the incidence of patients with neovascular macular degeneration because we selected people who spontaneously related a history of photopsias, rather than those in whom a history of photopsias was elicited specifically on questioning.
Migraine Migraine, accounting for 6% of eyes (12/215), is associated with photopsia morphology that differs considerably from what is described with other causes. Migraine, whether classic with a headache or purely ophthalmic with no headache, produces scintillating scotomas that are continuous. It produces photopsias that last for minutes at the edges of an often mobile scotoma. Although headaches often follow the photopsias in younger people, the former are commonly absent in the older population.44 These migraine “attacks” are characteristically bilateral, although patients commonly do not realize this is so until, when questioned, they remember they could not read, drive well, or recognize faces clearly during the episode. We thus question whether the entity of unilateral migraine is a real phenomenon or an entity in which there is underappreciation of photopsias in the second eye. Because migraine theoretically occurs as the result of vasoconstriction in the cerebrum, one would typically expect bilateral involvement. We are uncertain whether spasm and occlusion of the central retinal artery, a branch retinal artery, or the ophthalmic artery are causes in unilateral cases, In our experience, such occlusions typically produce rapid, generalized loss of vision, rather than scintillating scotomas that often travel across the visual field over minutes.6e8
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Anterior and Poster Retinal Stimulation It appears that pathologic entities that stimulate the retina anteriorly (vitreoretinal traction) most typically produce quick, temporal lightning flashes. Although the traction initially occurs on the anterior retina, we presume the photopsias still originate because of photoreceptor stimulation in the outer retina. In contrast, those conditions that stimulate photoreceptors from the posterior side of the retina (neovascular macular degeneration, retinitis pigmentosa, central serous chorioretinopathy, adult-onset foveal pigment epithelial dystrophy, multifocal choroiditis, Best’s disease) more typically produce central sparkles, twinkling, or strobes. We presume that retinal-derived photopsias originate in the photoreceptors, but differ depending on the type of stimulus. Nonetheless, we cannot be certain where the photopsias originate in the retina, because people with no light perception can still induce phosphenes by rubbing their eyes vigorously.45,46 Brain-derived photopsias typically occur as scintillating scotomas with migraine or central white flashes with vertebrobasilar insufficiency. Systemic causes (hypoglycemia, hyperglycemia, orthostatic hypotension, digitalis) tend to produce central or diffuse flickering. We are unsure whether photopsias arising from systemic causes occur primarily as the result of retinal stimulation or stimulation elsewhere along visual pathways in the brain. A photopsia history can be of help with management, especially when the cause of the photopsias in unclear. For example, the presence of accompanying headache, vertigo, and dizziness should raise suspicion of possible vertebrobasilar insufficiency. This is an important diagnosis to make; the authors have observed vertebrobasilar insufficiency leads to severe stroke with the “locked-in” syndrome. The presence of central photopsias suggests against vitreoretinal traction, because they occur in only 8% of such cases. Conversely, the sudden appearance of central twinkling, sparking, or strobes should raise the index of suspicion of choroidal neovascularization, because these photopsia features are present in 83% of cases.
Study Limitations As with any study, ours has potential drawbacks. Our data suggest a low sensitivity for a number of the disease entities (true-positives/(true-positives þ false-negatives) with photopsias, as well as a low specificity (true-negatives/(truenegatives þ false-positives) for a number of entities. In this regard, there may be overlap between different entities. For example, the central, quick, white flickering photopsias are similar with choroidal neovascularization and central serous chorioretinopathy, as are the temporal, quick, white photopsias found with PVD, retinal tears, and severe coughing. Furthermore, there is no gold standard for diagnosis for select diseases in the study. Our patient sample was drawn from a vitreoretinal referral practice. Thus, there may be artificially higher incidences of entities such as retinal detachment and retinal tears versus a series of consecutive patients with photopsias from a nonvitreoretinal practice.
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Photopsias: A Key to Diagnosis
In particular, the location of the photopsias is critical, with temporal photopsias suggesting vitreoretinal tractional phenomena, whereas central photopsias suggest macular diseases (neovascular macular degeneration, central serous chorioretinopathy, Best’s disease), central nervous system abnormalities (migraine, vertebrobasilar insufficiency, metastatic carcinoma), or systemic abnormalities (hypoglycemia, digitalis toxicity). Laterality is also especially helpful in that simultaneous bilateral photopsias suggest central nervous system abnormalities (migraine, vertebrobasilar insufficiency, papilledema, metastatic carcinoma, Charles Bonnet syndrome) or systemic conditions (hypoglycemia, hyperglycemia, severe coughing, orthostatic hypotension, digitalis toxicity). Characteristic patterns and features associated with different causes of photopsias are shown in Table 7. In summary, there is a wide range of variation in the morphology, color, duration, location, inciting stimuli, and accompanying systemic and ocular symptoms associated with photopsias. Although there is a considerable degree of crossover of symptoms, understanding the patterns most commonly associated with specific underlying conditions can help the clinician to ascertain the cause of photopsias with a greater degree of confidence.
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Footnotes and Financial Disclosures Originally received: May 4, 2015. Final revision: June 4, 2015. Accepted: June 17, 2015. Available online: August 3, 2015. Manuscript no. 2015-724. 1 Retina Service, Wills Eye Hospital, Jefferson Medical College, Philadelphia, Pennsylvania.
Author Contributions:
2
Overall responsibility: GC Brown, MM Brown, Fischer
3
Abbreviations and Acronyms: AMD ¼ age-related macular degeneration; PVD ¼ posterior vitreous detachment; RRD ¼ rhegmatogenous retinal detachment.
Research Unit, Wills Eye Hospital, Jefferson Medical College, Philadelphia, Pennsylvania.
Mid-Atlantic Retina, Plymouth Meeting, Pennsylvania. 4 Eye Research Institute, Philadelphia, Pennsylvania. 5
Center for Value-Based Medicine, Flourtown, Pennsylvania.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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Conception and design: GC Brown, MM Brown, Fischer Data collection: GC Brown, MM Brown, Fischer Analysis and interpretation: GC Brown, MM Brown, Fischer Obtained funding: Not applicable
Correspondence: Gary C. Brown, MD, MBA, Mid-Atlantic Retina, 4060 Butler Pike, Plymouth Meeting, PA 19462. E-mail: [email protected].