Adhering to international standards and maintaining retinal dark adaptation are critical to acquire valid full-field electroretinogram responses in the diagnosis and management of inherited retinal diseases. A practical protocol using a portable darkroom is provided to obtain full-field electroretinogram for infants and children under sedation or general anesthesia in the operating room setting.
Electroretinogram (ERG) is the only clinical objective test available to assess retinal function. Full-field ERG (ffERG) measures the panretinal rod and cone photoreceptor function as well as inner retinal function and is an important measure in the diagnosis and management of inherited retinal diseases as well as inflammatory, toxic, and nutritional retinopathies. Adhering to international standards and maintaining retinal dark adaptation are critical to acquire valid and reliable dark-adapted (scotopic) and light-adapted (photopic) ffERG responses. Performing ffERG in infants and children is challenging and often requires general anesthesia in the operating room. However, maintaining retinal dark adaptation in the operating room is becoming increasingly difficult given the numerous light sources from anesthesiology monitoring systems and other equipment. A practical and widely applicable method for ffERG testing is described in the operating room that optimizes retinal dark adaptation. The method reduces operating room time by dark-adapting the patient before general anesthesiology is instituted. The operating room is modified for dark adaptation and any remaining light source in the darkened operating room is minimized with the use of a modified portable foldable darkroom that encloses the patient’s head and the ERG examiner during ffERG scotopic recordings. The simple method adheres to ffERG international standards and provides valid reliable scotopic and photopic ffERG recordings that are critical to assess objective retinal function in this young age group where subjective assessment of visual function such as visual acuity and visual fields are not possible. Furthermore, the ffERG is the gold standard clinical test in detecting early onset inherited retinal diseases including Leber congenital amaurosis where approved gene therapy has become available. In sedated conditions, very low amplitude ffERG signals can be detected due to minimal orbicularis muscle activity interference, which is particularly relevant in patients after gene therapy to detect improved amplitude responses.
The electroretinogram (ERG) is the only clinical objective test available to assess retinal function and the full-field ERG (ffERG) is the only objective test to assess rod-photoreceptor generated activities1,2. The ffERG measures the electrical responses from the entire retina elicited by a full-field flash stimulus and is a gold standard test in the diagnosis and management of inherited retinal diseases2,3. Thus, the ffERG is an important test in infants and young children to detect early onset inherited retinal diseases such as Leber congenital amaurosis where approved gene therapy and clinical trials are available4,5.
Adherence to ffERG standards established by the International Society for Clinical Electrophysiology of Vision (ISCEV) are critical to acquire valid and reliable dark-adapted (scotopic) and light-adapted (photopic) ffERG responses1,3. Failure to properly maintain adequate retinal dark adaptation during scotopic ffERG recordings results in falsely-impaired recorded responses and patient mismanagement. Performing ffERG in infants and children is challenging given limited cooperation and often requires general anesthesia in the operating room6. A recent survey among ISCEV members showed 12-14% of ERG’s are performed under sedation or general anesthesia7. Maintaining retinal dark adaptation in the operating room is difficult given the numerous light sources from anesthesiology monitoring systems and other equipment. While anesthetic agents may have an effect in reducing ERG responses, ERG responses under sedation or general anesthesia are reliable in providing accurate diagnosis6,8,9.
A simple and widely applicable method is described for ffERG testing in the operating room that adheres to the international standards and optimizes retinal dark adaptation. The goal of this practical method is to provide valid reliable scotopic and photopic ffERG recordings to assess objective retinal function in infants and young children, which is particularly relevant in this young age group given subjective assessment of visual function such as visual acuity and visual fields are typically not possible. The operating room is modified to promote retinal dark adaptation, and the procedures reduce operating room time by dark-adapting the patient before sedation or general anesthesiology is instituted. A modified portable foldable darkroom encloses the patient’s head and the ERG examiner during ffERG scotopic recordings to minimize any remaining light source including light emission from the ERG system. The portable darkroom allows rapid access to the patient by the anesthesiologist when necessary. After the completion of ffERG, diagnostic retinal imaging including optical coherence tomography (OCT) and fundus imaging as well as venopuncture for genetic testing can easily be performed while the patient remains under anesthesia.
The method is suitable for practitioners and practices that manage pediatric patients with retinopathies. An average sized ocular operating room provides adequate space, and a room with low background electrical noise is desirable to allow quality ffERG recording. While the ERG examiner is inside the foldable darkroom during scotopic ffERG recording, a trained technician is needed to operate the ERG system outside of the foldable darkroom. Conferring with the anesthesiology team is essential in modifying the operating room and to promote the safety of the patient in a darkened environment.
The advantages of the method over alternative techniques include optimizing and maintaining retinal dark adaptation, promoting valid reliable ffERG recordings, improving patient safety, and facilitating additional diagnostic testing such as retinal imaging and venopuncture for genetic testing. Optimal dark adaptation is also critical given ffERG stimulators should be calibrated for complete darkness conditions as recommended by ISCEV10. Alternative methods include the use of oral agents such as chloral hydrate with variable sedative responses in infants and children, which affects the quality of ffERG recordings and causes difficulties in monitoring vital signs. While some children can cooperate with ffERG recording in the clinic, the testing session may be prolonged depending on cooperation, and the validity of ffERG recordings may be affected by eye movement and blink artifacts as well as difficulty in maintainng retinal dark adaptation4. The current method provides additional dark adaptation and safety measures compared to the previously described deep sedation ffERG method6.
The protocol follows the operating room guidelines of the Bascom Palmer Eye Institute, University of Miami and is applicable to infants, young children, and uncooperative adults. Patients who cannot have general anesthesia due to safety issues should not have the procedure.
1. Operating room selection and modification
2. Foldable portable darkroom selection and modification
3. Patient preparation and retinal dark adaption
4. Dark-Adapted full-field electroretinogram recording in the operating room
5. Light-Adapted full-field electroretinogram recording in the operating room
Using the method described, valid, reliable, interpretable normal and abnormal ffERG responses are feasibly obtained in the operating room for infants and young children under sedation or general anesthesia. In particular, falsely low scotopic ffERG responses are avoided, and common retinal causes of decreased vision and nystagmus in this age group are readily identified. For instance, the preservation of scotopic ffERG responses is important to differentiate Leber congenital amaurosis from achromatopsia where the cone ffERG responses are diminished in both conditions but the scotopic ffERG responses are preserved in achromatopsia but not in Leber congenital amaurosis (Figure 7). Obtaining good quality scotopic ffERG responses is also important to diagnose conditions where distinct scotopic ffERG waveform morphology is present. For example, the presence of a negative b-wave in the scotopic combined rod-cone ffERG response is a key feature of congenital stationary night blindness (Figure 7). While anesthetic agents may reduce ERG responses, ERG responses under anesthesia are reliable in providing accurate diagnosis.6 The lower limit of the normal range of the ERG responses is age dependent and increases with age. For instance, the lower limit of normal for age 12 months to 24 months for the scotopic rod responses with the Burian-Allen electrode is 75 µV. As recommended by ISCEV, individual ERG labs are encouraged to collect own normal values.
The method is used reliably to determine disease progression over time. For instance, the systemic features of Alström syndrome are subtle in very young patients and the initial ffERG responses may be similar to achromatopsia with relative preservation of scotopic ffERG responses and diminished cone responses (Figure 8). Over time, the scotopic ffERG responses worsen showing a cone-rod dysfunction pattern that is consistent with conditions including cone-rod dystrophy and secondary syndromic cone-rod degenerations such as Alström’s syndrome (Figure 8).
Figure 1: Dark proofing of openings of operating room. Opaque non-reflective black curtains cover operating room door and window openings. Please click here to view a larger version of this figure.
Figure 2A: Please click here to view a larger version of this figure.
Figure 2B: Folding portable darkroom. Commercially available foldable portable darkroom (A) isolates the patient’s head and the ERG examiner (B) to optimize the maintenance of retinal dark adaptation during scotopic ffERG recordings (photo taken with lights on before starting case for illustration purposes). Please click here to view a larger version of this figure.
Figure 3A: Please click here to view a larger version of this figure.
Figure 3B: Please click here to view a larger version of this figure.
Figure 3C: Modification of the rear of the darkroom. Small opening created at the rear of the darkroom (A) covered by double flaps (B) allow routing connections and cables to the ERG recording system outside of the darkroom (C). Please click here to view a larger version of this figure.
Figure 4: Dark adaptation with bilateral patching. A dark relaxation mask is placed over the patient after each eye is patched by placing a layer of black tape over 2 eye pads over closed eyelids. Please click here to view a larger version of this figure.
Figure 5A: Please click here to view a larger version of this figure.
Figure 5B: Dark proofing of operating room.
Translucent red filter films (A) are taped over monitors and opaque black tape (B) covers LEDs and light sources. Please click here to view a larger version of this figure.
Figure 6A: Please click here to view a larger version of this figure.
Figure 6B: Recoding scotopic ffERG responses inside darkroom.
Patient with darkroom in place (A). Scotopic ffERG responses are recorded in a very darkened environment inside darkroom (B) with a very dim red light mounted on a forehead band used to place corneal ERG recording electrodes in place (photo taken with lights on before starting case for illustration purposes). Please click here to view a larger version of this figure.
Figure 7: Normal and abnormal ffERG examples. Standard ffERG responses obtained with method in infants and young children showing normal responses and valid reliable scotopic and photopic responses that easily differentiate Leber congenital amaurosis (LCA), achromatopsia, and congenital stationary night blindness (CSNB). LCA example is a 6-year-old with RDH12 genotype; achromatopsia example is a 3-year-old with PDE6C genotype; CSNB example is a 3-year-old with TRPM1 genotype. Please click here to view a larger version of this figure.
Figure 8: ffERG example showing disease progression. Standard ffERG responses obtained with method obtained in a 2-year-old patient with follow-up 2 years later. Progression of the scotopic ffERG responses is evident, and patient was found to have Alström syndrome. Please click here to view a larger version of this figure.
The methodology and protocol describe how to effectively perform valid and reliable ffERG in infants and children under sedation or general anesthesia in the operating room. The major concept and aim of the technique are to provide and maintain optimal retinal dark adaptation during scotopic ffERG recordings. This is essential to provide accurate objective assessment of rod photoreceptor function given retinal dark adaptation is rapidly diminished by exposure even to dim light leading to erroneous recorded responses. The critical steps of the method are (i) to choose an operating room with low 60 Hz background electric current noise, proper electrical grounding and to modify and prepare the room meticulously to block light sources (ii) to pharmacologically dilated the pupils fully and to place multi-layer eye patches that completely blocks light to induce retinal dark adaptation (iii) to use a modified portable foldable darkroom that encloses the patient’s head and the ERG examiner, and (iv) to use the least amount of dim red light needed inside the darkroom during scotopic ffERG recording.
The method is significantly superior to existing alternative methods. While performing ffERG without sedation in infants less than 1 year old may be possible by using a feeding bottle and some children can cooperate with ffERG recording, cooperation is poor in most infants and young children. Performing ffERG with oral sedation in a conventional ERG recording darkroom lacks the ability to monitor the patient’s cardiopulmonary function safely and the spectrum of responses to the oral sedation is wide and unpredictable. Performing ffERG in a darkened operating room without a portable darkroom is typically not dark enough to adequately achieve and maintain dark adaptation given the growing number of new anesthetic and operating room equipment.
The method works well with a small handheld ffERG light stimulus given the limited space inside the portable darkroom, and ffERG recording is done one eye at a time. A larger full-size full-field ERG stimulus dome will allow simultaneous ERG recording of both eyes and shorten examination time. A full-size ERG stimulus dome would require a metallic arm to hold it securely over the supine patient and a larger portable darkroom with a much larger flap opening would be required to accommodate the metallic arm. Such modification is possible with care to create a large flap opening that is not prone to light leak.
Limitations of the method are few and include the effect of sedative and general anesthetic agents in reducing ERG responses, which is not substantial enough to influence accurate clinical diagnosis and follow-up testing to assess progression. The method requires the cooperation of the pediatric anesthesiology team to monitor patient in a dimly lit operating room for 15 minutes during scotopic ffERG recording. If anesthetic emergency arises, the procedure can be aborted immediately and the portable darkroom can be moved rapidly to allow full patient access.
The authors have nothing to disclose.
This paper is supported in part by the James V. Bastek, M.D. Hereditary Retinal Disease Research Program, Bascom Palmer Eye Institute, University of Miami, FL, USA; NIH Center Core Grant P30EY014801; Research to Prevent Blindness Unrestricted Award and Career Development Awards; Florida Lions Eye Bank and the Beauty of Sight Foundation, Miami, FL, USA; and Henri and Flore Lesieur Foundation.
Black tape | 3M Industrial Adhesives and Tapes Division, St Paul, MN 55144-1000 USA | 3M ID 70016070396 | |
Conduction and abrasive paste | Redux Paste (Electrolyte Paste) Hewlett Packard company, USA. Nuprep (Sking Prep Gel) and Ten20 (Conductive Neurodiagnostic Electrode Paste) Weaver and Company, CO, USA | 67-05 | |
Darkroom – Portable foldable | Scientex | B-LP1/B-LP1-X | Available in different sizes |
Dark adaptation mask (relaxation sleeping mask) | Mindfold Inc, Durango, CO, USA | 6576493 | Flexible black plastic face plate backed with a high-density soft foam padding that allows total darkness. |
Ear clips for electric grounding | Grass | F-E34DG-72 | Grass 10mm Gold Cup EEG Ear Clip with touchproof connector 72" wire – Set of 2 |
Electrodes ERG recording (Burian-Allen, DTL) | Burian-Allen, Hansen Ophthalmic Develoment Lab, Iowa, USA; DTL, Diagnosys, Lowell, MA 01854, USA. | 303-20LA, 303-20A, 303-20P, 303-20I, 303-20SI | Available in different sizes, requires modification as described in Protocol. |
ERG systems including handheld full-field stimulus | Any system meeting the standards established by the International Society for Clinical Electrophysiology of Vision (ISCEV). | Authors use Diagnosys and Roland systems; other ISCEV standard systems available. | |
Eye drops, propracaine, metilcellulose, phenilephrine, ciclopentolate, | Tropicamide 1% Phenylephrine 2.5% Cyclopentolate 1% Proparacaine 0.5% Akorn, Inc. Forest, IL 60045 GONIOTAIRE (Hypromellose 2.5%) Altaire Pharmaceuticals, Inc. NY, NY, USA 11931 | ||
Eye Patch | BSN Medical Inc, Rutherford College, NC | 46430-00 | Coverlet eye occlusor for treatment of lazy eye |
Head band with light | REMIX PRO. Princeton Tec, Trenton, NJ 08650 |
RMX300PRO-RD-BK | Requires placing layers of red filters over LED as described in protocol |